Cancers

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10 pages, 1166 KiB

Open AccessArticle

Photodynamic Therapy with an Association of Methylene Blue and Toluidine Blue Promoted a Synergic Effect against Oral Squamous Cell Carcinoma

by Évilin Rocha, Larissa Bomfim, Sérgio Junior, Gustavo Santos, Cássio Meira and Milena Soares

Cancers 2023, 15(23), 5509; https://doi.org/10.3390/cancers15235509 - 22 Nov 2023

Cited by 2 | Viewed by 1799

Abstract

Among the most malignant cancers, oral squamous cell carcinoma (OSCC) stands out as the most common malignant head and neck tumor. Despite advances in the field of treatment, the prognosis of patients with OSCC remains poor. Aiming to overcome the limitations of the [...] Read more.

Among the most malignant cancers, oral squamous cell carcinoma (OSCC) stands out as the most common malignant head and neck tumor. Despite advances in the field of treatment, the prognosis of patients with OSCC remains poor. Aiming to overcome the limitations of the currently existing therapies against OSCC, the present work aims to investigate the potential of photodynamic therapy (PDT) with phenothiazine derivatives used alone or in combination. The incorporation of methylene blue (MB) and toluidine blue (TB) was evaluated in OSCC cell lines (HSC-3 and SCC-9) and a nontumor cell line (Hfib). Both compounds exhibited concentration and time-dependent incorporation, with higher rates observed in tumor cells. Regarding dark-phase cytotoxic activity, SCC-9 cells were the most sensitive cell line with an IC₅₀ value of 362.6 µM and 41.4 µM for MB and TB, respectively. Using PDT, all lineages showed greater sensitivity, presenting lower IC₅₀ values when compared to the dark phase values. The combination index values of 0.69 (dark phase) and 0.73 (clear phase) associated with concave isobolograms, in both phases, revealed that MB and TB have synergistic effects when combined against SCC-9 cells. These findings suggest that MB or TB assisted with PDT holds promise for OSCC treatment. Full article

(This article belongs to the Special Issue Advances in Anticancer Drugs and Pharmacotherapy of Cancer)

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28 pages, 12195 KiB

Open AccessArticle

Discovery, Structure–Activity Relationship and In Vitro Anticancer Activity of Small-Molecule Inhibitors of the Protein–Protein Interactions between AF9/ENL and AF4 or DOT1L

by Xin Li, Xiaowei Wu, Shenyou Nie, Jidong Zhao, Yuan Yao, Fangrui Wu, Chandra Bhushan Mishra, Md Ashraf-Uz-Zaman, Bala Krishna Moku and Yongcheng Song

Cancers 2023, 15(21), 5283; https://doi.org/10.3390/cancers15215283 - 3 Nov 2023

Viewed by 1429

Abstract

Chromosomal translocations involving the mixed lineage leukemia (MLL) gene cause 5–10% acute leukemias with poor clinical outcomes. Protein–protein interactions (PPI) between the most frequent MLL fusion partner proteins AF9/ENL and AF4 or histone methyltransferase DOT1L are drug targets for MLL-rearranged (MLL-r) leukemia. Several [...] Read more.

Chromosomal translocations involving the mixed lineage leukemia (MLL) gene cause 5–10% acute leukemias with poor clinical outcomes. Protein–protein interactions (PPI) between the most frequent MLL fusion partner proteins AF9/ENL and AF4 or histone methyltransferase DOT1L are drug targets for MLL-rearranged (MLL-r) leukemia. Several benzothiophene-carboxamide compounds were identified as novel inhibitors of these PPIs with IC₅₀ values as low as 1.6 μM. Structure–activity relationship studies of 77 benzothiophene and related indole and benzofuran compounds show that a 4-piperidin-1-ylphenyl or 4-pyrrolidin-1-ylphenyl substituent is essential for the activity. The inhibitors suppressed expression of MLL target genes HoxA9, Meis1 and Myc, and selectively inhibited proliferation of MLL-r and other acute myeloid leukemia cells with EC₅₀ values as low as 4.7 μM. These inhibitors are useful chemical probes for biological studies of AF9/ENL, as well as pharmacological leads for further drug development against MLL-r and other leukemias. Full article

(This article belongs to the Special Issue Advances in Anticancer Drugs and Pharmacotherapy of Cancer)

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15 pages, 2318 KiB

Open AccessArticle

Palbociclib Combined with an Aromatase Inhibitor in Patients with Breast Cancer with Lung or Liver Metastases in US Clinical Practice

by Adam Brufsky, Xianchen Liu, Benjamin Li, Lynn McRoy, Connie Chen, Rachel M. Layman and Hope S. Rugo

Cancers 2023, 15(21), 5268; https://doi.org/10.3390/cancers15215268 - 2 Nov 2023

Viewed by 1998

Abstract

A cyclin-dependent kinase 4/6 inhibitor combined with endocrine therapy is the standard of care for patients with hormone receptor-positive/human epidermal growth factor 2-negative (HR+/HER2−) metastatic breast cancer (mBC), but real-world effectiveness data for patients with lung or liver metastases are limited. This retrospective [...] Read more.

A cyclin-dependent kinase 4/6 inhibitor combined with endocrine therapy is the standard of care for patients with hormone receptor-positive/human epidermal growth factor 2-negative (HR+/HER2−) metastatic breast cancer (mBC), but real-world effectiveness data for patients with lung or liver metastases are limited. This retrospective study included data from the US Flatiron Health database of patients with HR+/HER2− mBC and lung or liver metastases treated with first-line palbociclib (PAL) plus an aromatase inhibitor (AI) or an AI alone in routine clinical practice. Overall survival (OS) and real-world progression-free survival (rwPFS) were assessed. A total of 891 patients were included (622 with lung metastasis, 376 with liver metastasis, and 107 with both lung and liver metastasis). After stabilized inverse probability of treatment weighting to balance patient characteristics, PAL + AI versus AI alone was associated with significantly prolonged OS (HR = 0.62; p < 0.001) and rwPFS (HR = 0.55; p < 0.001) in patients with lung metastases and numerically longer OS (HR = 0.73; p = 0.056) and significantly longer rwPFS (HR = 0.57, p < 0.001) for those with liver metastases. Overall, PAL + AI versus AI alone was associated with prolonged OS and rwPFS in routine clinical practice, supporting the use of first-line PAL + AI for patients with HR+/HER2− mBC with lung and/or liver metastases. Full article

(This article belongs to the Special Issue Advances in Anticancer Drugs and Pharmacotherapy of Cancer)

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21 pages, 2271 KiB

Open AccessArticle

Optimization of a Luteolin-Loaded TPGS/Poloxamer 407 Nanomicelle: The Effects of Copolymers, Hydration Temperature and Duration, and Freezing Temperature on Encapsulation Efficiency, Particle Size, and Solubility

by Muhammad Redza Fahmi Mod Razif, Siok Yee Chan, Riyanto Teguh Widodo, Yik-Ling Chew, Masriana Hassan, Shairyzah Ahmad Hisham, Shamima Abdul Rahman, Long Chiau Ming, Ching Siang Tan, Siew-Keah Lee and Kai Bin Liew

Cancers 2023, 15(14), 3741; https://doi.org/10.3390/cancers15143741 - 24 Jul 2023

Cited by 5 | Viewed by 2076

Abstract

Background: Luteolin is a flavonoid compound that has been widely studied for its various anti-cancer properties and sensitization to multidrug-resistant cells. However, the limited solubility and bioavailability of Lut hindered its potential clinical use. Theoretically, the combination of this compound with vitamin E [...] Read more.

Background: Luteolin is a flavonoid compound that has been widely studied for its various anti-cancer properties and sensitization to multidrug-resistant cells. However, the limited solubility and bioavailability of Lut hindered its potential clinical use. Theoretically, the combination of this compound with vitamin E TPGS and poloxamer 407 can produce a synergistic effect to enhance tumor apoptosis and P-glycoprotein inhibition. This study aimed to develop and optimize vitamin E TPGS/Poloxamer 407 micelles loaded with luteolin through investigating certain factors that can affect the encapsulation efficiency and particle size of the micelle. Methods: A micelle was prepared using the film hydration method, and the micellar solution was lyophilized. The cake formed was analyzed. The factors investigated include the concentrations of the surfactants, ratio of vitamin E TPGS/Poloxamer 407, temperature of the hydrating solution, duration of hydration, and freezing temperature before lyophilization. The effects of these factors on the encapsulation efficiency and particle size of the micelle were also studied. The encapsulation efficiency was measured using a UV-Vis spectrophotometer, while particle size was measured using dynamic light scattering. Results: The optimized micelle was found to have 90% encapsulation efficiency with a particle size of less than 40 nm, which was achieved using a 10% concentration of surfactants at a vitamin E TPGS/Poloxamer 407 ratio of 3:1. The optimized temperature for hydrating the micellar film was 40 °C, the optimized mixing time was 1 h, and the optimized freezing temperature was −80 °C. The solubility of the luteolin-loaded micelles increased 459-fold compared to pure Lut in water. The critical micelle concentration of the vitamin E TPGS/Poloxamer 407 micelle was 0.001 mg/mL, and the release study showed that luteolin-loaded micelles exhibited sustained release behavior. The release of luteolin from a micelle was found to be higher in pH 6.8 compared to pH 7.4, which signified that luteolin could be accumulated more in a tumor microenvironment compared to blood. Conclusion: This study demonstrated that several factors need to be considered when developing such nanoparticles in order to obtain a well-optimized micelle. Full article

(This article belongs to the Special Issue Advances in Anticancer Drugs and Pharmacotherapy of Cancer)

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24 pages, 7443 KiB

Open AccessArticle

Synthesis of New Chromene Derivatives Targeting Triple-Negative Breast Cancer Cells

by Aysha Alneyadi, Zohra Nausheen Nizami, Hanan E. Aburawi, Soleiman Hisaindee, Muhammad Nawaz, Samir Attoub, Gaber Ramadan, Nehla Benhalilou, Mazoun Al Azzani, Yassine Elmahi, Aysha Almeqbali, Khalid Muhammad, Ali H. Eid, Ranjit Vijayan and Rabah Iratni

Cancers 2023, 15(10), 2682; https://doi.org/10.3390/cancers15102682 - 9 May 2023

Cited by 6 | Viewed by 3150

Abstract

Breast cancer continues to be the leading cause of cancer-related deaths among women worldwide. The most aggressive type of breast cancer is triple-negative breast cancer (TNBC). Indeed, not only does TNBC not respond well to several chemotherapeutic agents, but it also frequently develops [...] Read more.

Breast cancer continues to be the leading cause of cancer-related deaths among women worldwide. The most aggressive type of breast cancer is triple-negative breast cancer (TNBC). Indeed, not only does TNBC not respond well to several chemotherapeutic agents, but it also frequently develops resistance to various anti-cancer drugs, including taxane mitotic inhibitors. This necessitates the search for newer, more efficacious drugs. In this study, we synthesized two novel chromene derivatives (C1 and C2) and tested their efficacy against a battery of luminal type A and TNBC cell lines. Our results show that C1 and C2 significantly and specifically inhibited TNBC cell viability but had no effect on the luminal A cell type. In addition, these novel compounds induced mitotic arrest, cell multinucleation leading to senescence, and apoptotic cell death through the activation of the extrinsic pathway. We also showed that the underlying mechanisms for these actions of C1 and C2 involved inhibition of microtubule polymerization and disruption of the F-actin cytoskeleton. Furthermore, both compounds significantly attenuated migration of TNBC cells and inhibited angiogenesis in vitro. Finally, we performed an in silico analysis, which revealed that these novel variants bind to the colchicine binding site in β-tubulin. Taken together, our data highlight the potential chemotherapeutic properties of two novel chromene compounds against TNBC. Full article

(This article belongs to the Special Issue Advances in Anticancer Drugs and Pharmacotherapy of Cancer)

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11 pages, 9507 KiB

Open AccessArticle

Discovery of Novel Bioactive Tanshinones and Carnosol Analogues against Breast Cancer

by Miguel A. González-Cardenete, Natalia González-Zapata, Lucinda Boyd and Fatima Rivas

Cancers 2023, 15(4), 1318; https://doi.org/10.3390/cancers15041318 - 19 Feb 2023

Cited by 6 | Viewed by 2898

Abstract

The abietane diterpenoids ferruginol (1), tanshinone IIA (3), and carnosol (4) are well-known for their interesting pharmacological properties, including antitumor, similar to other natural and semisynthetic abietanes. In this study, a pair of semisynthetic C18-functionalized analogues of [...] Read more.

The abietane diterpenoids ferruginol (1), tanshinone IIA (3), and carnosol (4) are well-known for their interesting pharmacological properties, including antitumor, similar to other natural and semisynthetic abietanes. In this study, a pair of semisynthetic C18-functionalized analogues of 3 and 4 were prepared from the commercially available (+)-dehydroabietylamine or readily obtained methyl dehydroabietate. Semisynthetic ferruginol (1) and some selected analogues, together with the synthesized analogues, were tested in vitro for the inhibition of proliferation in four breast cancer cell lines, SUM149, MDA-MB231, T47D, and MCF07. As a result, several tested abietane analogues decreased cell proliferation and enhanced cell death, with IC₅₀ in the range 1.3–18.7 μM. This work demonstrates the antitumor activities of two tested compounds, making these molecules interesting for the development of new anticancer agents. Full article

(This article belongs to the Special Issue Advances in Anticancer Drugs and Pharmacotherapy of Cancer)

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13 pages, 1355 KiB

Open AccessArticle

Toxicity of Asciminib in Real Clinical Practice: Analysis of Side Effects and Cross-Toxicity with Tyrosine Kinase Inhibitors

by Lucía Pérez-Lamas, Alejandro Luna, Concepción Boque, Blanca Xicoy, Pilar Giraldo, Raúl Pérez López, Concepción Ruiz Nuño, Natalia De las Heras, Elvira Mora Casterá, Javier López Marín, Adrián Segura Díaz, Valle Gómez, Patricia Vélez Tenza, Magdalena Sierra Pacho, Juan Antonio Vera Goñi, Melania Moreno Vega, Alberto Alvarez-Larrán, Montse Cortés, Manuel Pérez Encinas, Patricia Carrascosa Mastell, Anna Angona, Ana Rosell, Sunil Lakhwani, Mercedes Colorado, Elena Ramila, Carlos Cervero, Beatriz Cuevas, Lucía Villalón Blanco, Raquel de Paz, Antonio Paz Coll, María José Fernández, Luis Felipe Casado, Juan Manuel Alonso-Domínguez, María Magdalena Anguita Arance, Araceli Salamanca Cuenca, Antonio Jiménez-Velasco, Santiago Osorio Prendes, Marta Santaliestra, María José Lis Chulvi, Juan Carlos Hernández-Boluda and Valentín García-Gutiérrez Show full author list Hide full author list

Cancers 2023, 15(4), 1045; https://doi.org/10.3390/cancers15041045 - 7 Feb 2023

Cited by 6 | Viewed by 4187

Abstract

(1) Background: Despite the prognostic improvements achieved with tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML), a minority of patients still fail TKIs. The recent introduction of asciminib may be a promising option in intolerant patients, as it is a first-in-class inhibitor [...] Read more.

(1) Background: Despite the prognostic improvements achieved with tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML), a minority of patients still fail TKIs. The recent introduction of asciminib may be a promising option in intolerant patients, as it is a first-in-class inhibitor with a more selective mechanism of action different from the ATP-competitive inhibition that occurs with TKIs. Therefore, our goal was to analyze toxicities shown with asciminib as well as to study cross-toxicity with previous TKIs. (2) Methods: An observational, multicenter, retrospective study was performed with data from 77 patients with CML with therapeutic failure to second-generation TKIs who received asciminib through a managed-access program (MAP) (3) Results: With a median follow-up of 13.7 months, 22 patients (28.5%) discontinued treatment: 32% (7/22) due to intolerance and 45% (10/22) due to resistance. Fifty-five percent of the patients reported adverse effects (AEs) with asciminib and eighteen percent grade 3–4. Most frequent AEs were: fatigue (18%), thrombocytopenia (17%), anemia (12%), and arthralgias (12%). None of the patients experienced cardiovascular events or occlusive arterial disease. Further, 26%, 25%, and 9% of patients required dose adjustment, temporary suspension, or definitive discontinuation of treatment, respectively. Toxicities under asciminib seemed lower than with prior TKIs for anemia, cardiovascular events, pleural/pericardial effusion, diarrhea, and edema. Cross-toxicity risk was statistically significant for thrombocytopenia, anemia, neutropenia, fatigue, vomiting, and pancreatitis. (4) Conclusion: Asciminib is a molecule with a good safety profile and with a low rate of AEs. However, despite its new mechanism of action, asciminib presents a risk of cross-toxicity with classical TKIs for some AEs. Full article

(This article belongs to the Special Issue Advances in Anticancer Drugs and Pharmacotherapy of Cancer)

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20 pages, 4413 KiB

Open AccessArticle

Inhibition of Macropinocytosis Enhances the Sensitivity of Osteosarcoma Cells to Benzethonium Chloride

by Haichao Xia, Yanran Huang, Lulu Zhang, Lijuan Luo, Xiaoxuan Wang, Qiuping Lu, Jingtao Xu, Chunmei Yang, Habu Jiwa, Shiqiong Liang, Liping Xie, Xiaoji Luo and Jinyong Luo

Cancers 2023, 15(3), 961; https://doi.org/10.3390/cancers15030961 - 2 Feb 2023

Cited by 4 | Viewed by 2550

Abstract

Osteosarcoma (OS) is a primary malignant tumor of bone. Chemotherapy is one of the crucial approaches to prevent its metastasis and improve prognosis. Despite continuous improvements in the clinical treatment of OS, tumor resistance and metastasis remain dominant clinical challenges. Macropinocytosis, a form [...] Read more.

Osteosarcoma (OS) is a primary malignant tumor of bone. Chemotherapy is one of the crucial approaches to prevent its metastasis and improve prognosis. Despite continuous improvements in the clinical treatment of OS, tumor resistance and metastasis remain dominant clinical challenges. Macropinocytosis, a form of non-selective nutrient endocytosis, has received increasing attention as a novel target for cancer therapy, yet its role in OS cells remains obscure. Benzethonium chloride (BZN) is an FDA-approved antiseptic and bactericide with broad-spectrum anticancer effects. Here, we described that BZN suppressed the proliferation, migration, and invasion of OS cells in vitro and in vivo, but simultaneously promoted the massive accumulation of cytoplasmic vacuoles as well. Mechanistically, BZN repressed the ERK1/2 signaling pathway, and the ERK1/2 activator partially neutralized the inhibitory effect of BZN on OS cells. Subsequently, we demonstrated that vacuoles originated from macropinocytosis and indicated that OS cells might employ macropinocytosis as a compensatory survival mechanism in response to BZN. Remarkably, macropinocytosis inhibitors enhanced the anti-OS effect of BZN in vitro and in vivo. In conclusion, our results suggest that BZN may inhibit OS cells by repressing the ERK1/2 signaling pathway and propose a potential strategy to enhance the BZN-induced inhibitory effect by suppressing macropinocytosis. Full article

(This article belongs to the Special Issue Advances in Anticancer Drugs and Pharmacotherapy of Cancer)

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23 pages, 11022 KiB

Open AccessArticle

Multi-Fold Computational Analysis to Discover Novel Putative Inhibitors of Isethionate Sulfite-Lyase (Isla) from Bilophila wadsworthia: Combating Colorectal Cancer and Inflammatory Bowel Diseases

by Muhammad Waqas, Sobia Ahsan Halim, Atta Ullah, Assim Alaa Mohammed Ali, Asaad Khalid, Ashraf N. Abdalla, Ajmal Khan and Ahmed Al-Harrasi

Cancers 2023, 15(3), 901; https://doi.org/10.3390/cancers15030901 - 31 Jan 2023

Cited by 10 | Viewed by 2865

Abstract

A glycal radical enzyme called isethionate sulfite-lyase (Isla) breaks the C–S bond in isethionate to produce acetaldehyde and sulfite. This enzyme was found in the Gram-negative, colonial Bilophila wadsworthia bacteria. Sulfur dioxide, acetate, and ammonia are produced by the anaerobic respiration route from [...] Read more.

A glycal radical enzyme called isethionate sulfite-lyase (Isla) breaks the C–S bond in isethionate to produce acetaldehyde and sulfite. This enzyme was found in the Gram-negative, colonial Bilophila wadsworthia bacteria. Sulfur dioxide, acetate, and ammonia are produced by the anaerobic respiration route from (sulfonate isethionate). Strong genotoxic H₂S damages the colon’s mucous lining, which aids in the development of colorectal cancer. H₂S production also contributes to inflammatory bowel diseases such as colitis. Here, we describe the structure-based drug designing for the Isla using an in-house database of naturally isolated compounds and synthetic derivatives. In structure-based drug discovery, a combination of methods was used, including molecular docking, pharmacokinetics properties evaluation, binding free energy calculations by the molecular mechanics/generalized born surface area (MM/GBSA) method, and protein structure dynamics exploration via molecular dynamic simulations, to retrieve novel and putative inhibitors for the Isla protein. Based on the docking score, six compounds show significant binding interaction with the Isla active site crucial residues and exhibit drug-like features, good absorption, distribution, metabolism, and excretion profile with no toxicity. The binding free energy reveals that these compounds have a strong affinity with the Isla. In addition, the molecular dynamics simulations reveal that these compounds substantially affect the protein structure dynamics. As per our knowledge, this study is the first attempt to discover Isla potential inhibitors. The compounds proposed in the study using a multi-fold computational technique may be verified in vitro as possible inhibitors of Isla and possess the potential for the future development of new medications that target Isla. Full article

(This article belongs to the Special Issue Advances in Anticancer Drugs and Pharmacotherapy of Cancer)

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17 pages, 3112 KiB

Open AccessArticle

Naturally Isolated Sesquiterpene Lactone and Hydroxyanthraquinone Induce Apoptosis in Oral Squamous Cell Carcinoma Cell Line

by Afshan Shams, Ayaz Ahmed, Ajmal Khan, Shariqa Khawaja, Najeeb Ur Rehman, Asma Saleem Qazi, Adnan Khan, Sami Bawazeer, Syed Abid Ali and Ahmed Al-Harrasi

Cancers 2023, 15(2), 557; https://doi.org/10.3390/cancers15020557 - 16 Jan 2023

Cited by 5 | Viewed by 2964

Abstract

Oral squamous cell carcinoma (OSCC) is one of the most prevalent cancers worldwide, especially in Asian countries. The emergence of its drug resistance and its side effects demands alternatives, to improve prognosis. Since the majority of cancer drugs are derived from natural sources, [...] Read more.

Oral squamous cell carcinoma (OSCC) is one of the most prevalent cancers worldwide, especially in Asian countries. The emergence of its drug resistance and its side effects demands alternatives, to improve prognosis. Since the majority of cancer drugs are derived from natural sources, it provides a window to look for more biocompatible alternatives. In this study, two natural compounds, costunolide (CE) and aloe emodin (AE), were isolated from the stem of Lycium shawii. The compounds were examined for their anticancer and apoptotic potentials against OSCC (CAL 27) cells, using an in vitro analysis, such as a MTT assay, scratch assay, gene, and protein expressions. Both compounds, CE and AE, were found to be cytotoxic against the cancer cells with an IC₅₀ value of 32 and 38 µM, respectively. Moreover, the compounds were found to be non-toxic against normal NIH-3T3 cells and comparable with the standard drug i.e., 5-fluorouracil (IC₅₀ = 97.76 µM). These compounds were active against normal cells at higher concentrations. Nuclear staining displayed the presence of apoptosis-associated morphological changes, i.e., karyopyknosis and karyorrhexis in the treated cancer cells. Flow cytometry results further confirmed that these compounds induce apoptosis rather than necrosis, as the majority of the cells were found in the late apoptotic phase. Gene and protein expression analyses showed an increased expression of apoptotic genes, i.e., BAK, caspase 3, 6, and 9. Moreover, the compounds significantly downregulated the expression of the anti-apoptotic (BCL-2 L1), metastatic (MMP-2), and pro-inflammatory (COX-2) genes. Both compounds have shown promising anticancer, apoptotic, and anti-migratory activities against the OSCC cell line (i.e., CAL-27). However, further in vivo studies are required to explore these compounds as anticancer agents. Full article

(This article belongs to the Special Issue Advances in Anticancer Drugs and Pharmacotherapy of Cancer)

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20 pages, 5984 KiB

Open AccessArticle

Phytochemical Compounds and Anticancer Activity of Cladanthus mixtus Extracts from Northern Morocco

by Amina El Mihyaoui, Saoulajan Charfi, El Hadi Erbiai, Mariana Pereira, Diana Duarte, Nuno Vale, María Emilia Candela Castillo, Alain Badoc, Ahmed Lamarti, Joaquim C. G. Esteves da Silva and Marino B. Arnao

Cancers 2023, 15(1), 152; https://doi.org/10.3390/cancers15010152 - 27 Dec 2022

Cited by 8 | Viewed by 2930

Abstract

Many of the chemotherapeutic drugs for the treatment of cancer are molecules identified and isolated from plants or their synthetic derivatives. This work aimed to identify the bioactive compounds using LC-MS and GC-MS and to evaluate the anticancer activity of the methanolic extracts [...] Read more.

Many of the chemotherapeutic drugs for the treatment of cancer are molecules identified and isolated from plants or their synthetic derivatives. This work aimed to identify the bioactive compounds using LC-MS and GC-MS and to evaluate the anticancer activity of the methanolic extracts of roots, stems, leaves, and flowers from Cladanthus mixtus. The anticancer activity was evaluated in vitro against two cancer cell lines: human breast carcinoma (MCF-7) and human prostate carcinoma (PC-3), using the MTT assay and microscopic observation. A human normal lung fibroblast (MRC-5) was included to determine the extract’s safety for non-tumoral cells. The chemical composition results by LC-MS analysis revealed the presence of 24 phenolic compounds. Furthermore, GC-MS analysis allowed the identification of many biomolecules belonging to terpenoids, esters, alcohols, alkanes, fatty acids, organic acids, benzenes, phenols, ketones, carbonyls, amines, sterols, and other groups. The findings suggest that the majority of C. mixtus extracts have antiproliferative activity against two cancer cell lines, MCF-7 and PC-3, and one non-tumoral cell line, MRC-5. The activity was dose-dependent, and the highest effect was obtained with leaf extract in the two cancer cell lines. Moreover, these extracts demonstrated an acceptable toxicological profile against normal cells. Overall, C. mixtus extracts revealed promising antitumor properties provided by their phytochemical composition. Full article

(This article belongs to the Special Issue Advances in Anticancer Drugs and Pharmacotherapy of Cancer)

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32 pages, 3691 KiB

Open AccessEditor’s ChoiceArticle

Targets, Mechanisms and Cytotoxicity of Half-Sandwich Ir(III) Complexes Are Modulated by Structural Modifications on the Benzazole Ancillary Ligand

by M. Isabel Acuña, Ana R. Rubio, Marta Martínez-Alonso, Natalia Busto, Ana María Rodríguez, Nerea Davila-Ferreira, Carl Smythe, Gustavo Espino, Begoña García and Fernando Domínguez

Cancers 2023, 15(1), 107; https://doi.org/10.3390/cancers15010107 - 24 Dec 2022

Cited by 5 | Viewed by 4099

Abstract

Cancers are driven by multiple genetic mutations but evolve to evade treatments targeting specific mutations. Nonetheless, cancers cannot evade a treatment that targets mitochondria, which are essential for tumor progression. Iridium complexes have shown anticancer properties, but they lack specificity for their intracellular [...] Read more.

Cancers are driven by multiple genetic mutations but evolve to evade treatments targeting specific mutations. Nonetheless, cancers cannot evade a treatment that targets mitochondria, which are essential for tumor progression. Iridium complexes have shown anticancer properties, but they lack specificity for their intracellular targets, leading to undesirable side effects. Herein we present a systematic study on structure-activity relationships of eight arylbenzazole-based Iridium(III) complexes of type [IrCl(Cp*)], that have revealed the role of each atom of the ancillary ligand in the physical chemistry properties, cytotoxicity and mechanism of biological action. Neutral complexes, especially those bearing phenylbenzimidazole (HL1 and HL2), restrict the binding to DNA and albumin. One of them, complex 1[C,NH-Cl], is the most selective one, does not bind DNA, targets exclusively the mitochondria, disturbs the mitochondria membrane permeability inducing proton leak and increases ROS levels, triggering the molecular machinery of regulated cell death. In mice with orthotopic lung tumors, the administration of complex 1[C,NH-Cl] reduced the tumor burden. Cancers are more vulnerable than normal tissues to a treatment that harnesses mitochondrial dysfunction. Thus, complex 1[C,NH-Cl] characterization opens the way to the development of new compounds to exploit this vulnerability. Full article

(This article belongs to the Special Issue Advances in Anticancer Drugs and Pharmacotherapy of Cancer)

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17 pages, 3175 KiB

Open AccessArticle

Efficient Synthesis with Green Chemistry Approach of Novel Pharmacophores of Imidazole-Based Hybrids for Tumor Treatment: Mechanistic Insights from In Situ to In Silico

by Majid Khan, Syed Raza Shah, Faizullah Khan, Sobia Ahsan Halim, Shaikh Mizanoor Rahman, Mohammad Khalid, Ajmal Khan and Ahmed Al-Harrasi

Cancers 2022, 14(20), 5079; https://doi.org/10.3390/cancers14205079 - 17 Oct 2022

Cited by 7 | Viewed by 1938

Abstract

Imidazole-based pyrimidine hybrids are considered a remarkable class of compounds in pharmaceutical chemistry. Here, we report the anticancer bioactivities of eleven imidazole-based pyrimidine hybrids (1–11) that specifically target cytosolic carbonic anhydrase (CAs) isoenzymes, including human CA-II and human CA-IX [...] Read more.

Imidazole-based pyrimidine hybrids are considered a remarkable class of compounds in pharmaceutical chemistry. Here, we report the anticancer bioactivities of eleven imidazole-based pyrimidine hybrids (1–11) that specifically target cytosolic carbonic anhydrase (CAs) isoenzymes, including human CA-II and human CA-IX (hCA-II, and hCA-IX). A highly eco-friendly aqueous approach was used for the formation of a carbon–carbon bond by reacting aromatic nitro group substitution of nitroimidazoles with carbon nucleophiles. The in vitro results indicate that this new class of compounds (1–11) includes significant inhibitors of hCA IX with IC₅₀ values in the range of 9.6 ± 0.2–32.2 ± 1.0 µM, while hCA II showed IC₅₀ values in range of 11.6 ± 0.2–31.1 ± 1.3 µM. Compound 2 (IC₅₀ = 12.3 ± 0.1 µM) showed selective inhibition for hCA-II while 7, 8, and 10 (IC₅₀ = 9.6–32.2 µM) were selective for hCA-IX. The mechanism of action was investigated through in vitro kinetics studies that revealed that compounds 7, 3, 11, 10, 4, and 9 for CA-IX and 1, 2, and 11 for CA-II are competitive inhibitors with dissociation constant (Ki) in the range of 7.32–17.02 µM. Furthermore, the in situ cytotoxicity of these compounds was investigated in the human breast cancer cell line MDA-MB-231 and compared with the normal human breast cell line, MCF-10A. Compound 5 showed excellent anticancer/cytotoxic activity in MDA-MB-231 with no toxicity to the normal breast cells. In addition, in silico molecular docking was employed to predict the binding mechanism of active compounds with their targets. This in silico observation aligned with our experimental results. Our findings signify that imidazole-based hybrids could be a useful choice to design anticancer agents for breast and lung tumors, or antiglaucoma compounds, by specific inhibition of carbonic anhydrases. Full article

(This article belongs to the Special Issue Advances in Anticancer Drugs and Pharmacotherapy of Cancer)

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Review

Jump to: Research, Other

12 pages, 631 KiB

Open AccessReview

The Role of Anesthetic Drugs and Statins in Prostate Cancer Recurrence: Starting at the Actual Knowledge and Walking through a New Paradigm

by Aida Raigon Ponferrada, Juan Carlos Molina Ruiz, Salvador Romero Molina, Verónica Rodriguez Garcia and Jose Luis Guerrero Orriach

Cancers 2023, 15(11), 3059; https://doi.org/10.3390/cancers15113059 - 5 Jun 2023

Viewed by 1548

Abstract

Prostate cancer has become a major health problem in men. Its incidence is increasing as the average age of the affected population tends to be higher. Of all the possible treatments, surgery is the gold standard in its treatment. Surgery produces a deregulation [...] Read more.

Prostate cancer has become a major health problem in men. Its incidence is increasing as the average age of the affected population tends to be higher. Of all the possible treatments, surgery is the gold standard in its treatment. Surgery produces a deregulation in the immune system that can favour the development of distant metastases. Different anesthetic techniques have raised the hypothesis that different anesthetic drugs influence tumor recurrence and prognosis. Some mechanisms are beginning to be understood by which halogenated agents in cancer patients and the use of opioids may negatively affect patients. In this document, we group together all the available evidence on how the different anesthetic drugs affect tumor recurrence in prostate cancer. Full article

(This article belongs to the Special Issue Advances in Anticancer Drugs and Pharmacotherapy of Cancer)

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35 pages, 1850 KiB

Open AccessReview

Reviewing the Prospective Pharmacological Potential of Isothiocyanates in Fight against Female-Specific Cancers

by Shoaib Shoaib, Farheen Badrealam Khan, Meshari A. Alsharif, M. Shaheer Malik, Saleh A. Ahmed, Yahya F. Jamous, Shahab Uddin, Ching Siang Tan, Chrismawan Ardianto, Saba Tufail, Long Chiau Ming, Nabiha Yusuf and Najmul Islam

Cancers 2023, 15(8), 2390; https://doi.org/10.3390/cancers15082390 - 20 Apr 2023

Cited by 5 | Viewed by 3327

Abstract

Gynecological cancers are the most commonly diagnosed malignancies in females worldwide. Despite the advancement of diagnostic tools as well as the availability of various therapeutic interventions, the incidence and mortality of female-specific cancers is still a life-threatening issue, prevailing as one of the [...] Read more.

Gynecological cancers are the most commonly diagnosed malignancies in females worldwide. Despite the advancement of diagnostic tools as well as the availability of various therapeutic interventions, the incidence and mortality of female-specific cancers is still a life-threatening issue, prevailing as one of the major health problems worldwide. Lately, alternative medicines have garnered immense attention as a therapeutic intervention against various types of cancers, seemingly because of their safety profiles and enhanced effectiveness. Isothiocyanates (ITCs), specifically sulforaphane, benzyl isothiocyanate, and phenethyl isothiocyanate, have shown an intriguing potential to actively contribute to cancer cell growth inhibition, apoptosis induction, epigenetic alterations, and modulation of autophagy and cancer stem cells in female-specific cancers. Additionally, it has been shown that ITCs plausibly enhance the chemo-sensitization of many chemotherapeutic drugs. To this end, evidence has shown enhanced efficacy in combinatorial regimens with conventional chemotherapeutic drugs and/or other phytochemicals. Reckoning with these, herein, we discuss the advances in the knowledge regarding the aspects highlighting the molecular intricacies of ITCs in female-specific cancers. In addition, we have also argued regarding the potential of ITCs either as solitary treatment or in a combinatorial therapeutic regimen for the prevention and/or treatment of female-specific cancers. Hopefully, this review will open new horizons for consideration of ITCs in therapeutic interventions that would undoubtedly improve the prognosis of the female-specific cancer clientele. Considering all these, it is reasonable to state that a better understanding of these molecular intricacies will plausibly provide a facile opportunity for treating these female-specific cancers. Full article

(This article belongs to the Special Issue Advances in Anticancer Drugs and Pharmacotherapy of Cancer)

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28 pages, 5172 KiB

Open AccessReview

Baicalein as Promising Anticancer Agent: A Comprehensive Analysis on Molecular Mechanisms and Therapeutic Perspectives

by A K M Helal Morshed, Supti Paul, Arafat Hossain, Tuli Basak, Md. Sanower Hossain, Md. Mehedi Hasan, Md. Al Hasibuzzaman, Tanjim Ishraq Rahaman, Md. Abdur Rashid Mia, Pollob Shing, Md Sohel, Shabana Bibi, Dipta Dey, Partha Biswas, Md. Nazmul Hasan, Long Chiau Ming and Ching Siang Tan

Cancers 2023, 15(7), 2128; https://doi.org/10.3390/cancers15072128 - 3 Apr 2023

Cited by 30 | Viewed by 5778

Abstract

Despite significant therapeutic advancements for cancer, an atrocious global burden (for example, health and economic) and radio- and chemo-resistance limit their effectiveness and result in unfavorable health consequences. Natural compounds are generally considered safer than synthetic drugs, and their use in cancer treatment [...] Read more.

Despite significant therapeutic advancements for cancer, an atrocious global burden (for example, health and economic) and radio- and chemo-resistance limit their effectiveness and result in unfavorable health consequences. Natural compounds are generally considered safer than synthetic drugs, and their use in cancer treatment alone, or in combination with conventional therapies, is increasingly becoming accepted. Interesting outcomes from pre-clinical trials using Baicalein in combination with conventional medicines have been reported, and some of them have also undergone clinical trials in later stages. As a result, we investigated the prospects of Baicalein, a naturally occurring substance extracted from the stems of Scutellaria baicalensis Georgi and Oroxylum indicum Kurz, which targets a wide range of molecular changes that are involved in cancer development. In other words, this review is primarily driven by the findings from studies of Baicalein therapy in several cancer cell populations based on promising pre-clinical research. The modifications of numerous signal transduction mechanisms and transcriptional agents have been highlighted as the major players for Baicalein’s anti-malignant properties at the micro level. These include AKT serine/threonine protein kinase B (AKT) as well as PI3K/Akt/mTOR, matrix metalloproteinases-2 & 9 (MMP-2 & 9), Wnt/-catenin, Poly(ADP-ribose) polymerase (PARP), Mitogen-activated protein kinase (MAPK), NF-κB, Caspase-3/8/9, Smad4, Notch 1/Hes, Signal transducer and activator of transcription 3 (STAT3), Nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein-1 (Keap 1), Adenosine monophosphate-activated protein kinase (AMPK), Src/Id1, ROS signaling, miR 183/ezrin, and Sonic hedgehog (Shh) signaling cascades. The promise of Baicalein as an anti-inflammatory to anti-apoptotic/anti-angiogenic/anti-metastatic medicinal element for treating various malignancies and its capability to inhibit malignant stem cells, evidence of synergistic effects, and design of nanomedicine-based drugs are altogether well supported by the data presented in this review study. Full article

(This article belongs to the Special Issue Advances in Anticancer Drugs and Pharmacotherapy of Cancer)

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19 pages, 414 KiB

Open AccessReview

Evaluation of Delayed-Type Hypersensitivity to Antineoplastic Drugs—An Overview

by Inés Roger, Paula Montero, Martín Pérez-Leal, Javier Milara and Julio Cortijo

Cancers 2023, 15(4), 1208; https://doi.org/10.3390/cancers15041208 - 14 Feb 2023

Viewed by 2356

Abstract

Nowadays, clinical practice encounters the problem of delayed-type hypersensitivity (DTH) induced by several drugs. Antineoplastic treatments are among the drugs which show an elevated proportion of DHT reactions, leading to the worsening of patients’ quality of life. The range of symptoms in DHT [...] Read more.

Nowadays, clinical practice encounters the problem of delayed-type hypersensitivity (DTH) induced by several drugs. Antineoplastic treatments are among the drugs which show an elevated proportion of DHT reactions, leading to the worsening of patients’ quality of life. The range of symptoms in DHT reactions can vary from mild, such as self-limiting maculopapular eruptions, to severe, such as Stevens–Johnson Syndrome. The development of these reactions supposes a negative impact, not only by limiting patients’ quality of life, but also leading to economic loss due to market withdrawal of the affected drugs and high hospitalization costs. However, despite this problem, there are no available standard in vitro or in vivo methods that allow for the evaluation of the sensitizing potential of drugs in the preclinical phase. Therefore, the aim of this review is to summarize the skin reactions caused by the different antineoplastic families, followed by a comprehensive evaluation of the in vitro and in vivo methods used to detect DTHs and that could be suitable to test antineoplastic hypersensitivity reactions. Full article

(This article belongs to the Special Issue Advances in Anticancer Drugs and Pharmacotherapy of Cancer)

30 pages, 2931 KiB

Open AccessReview

Seaweed-Derived Sulfated Polysaccharides; The New Age Chemopreventives: A Comprehensive Review

by Prajna Paramita Bhuyan, Rabindra Nayak, Srimanta Patra, Hadi Sajid Abdulabbas, Mrutyunjay Jena and Biswajita Pradhan

Cancers 2023, 15(3), 715; https://doi.org/10.3390/cancers15030715 - 24 Jan 2023

Cited by 15 | Viewed by 3936

Abstract

Seaweed-derived bioactive compounds are regularly employed to treat human diseases. Sulfated polysaccharides are potent chemotherapeutic or chemopreventive medications since it has been discovered. They have exhibited anti-cancer properties by enhancing immunity and driving apoptosis. Through dynamic modulation of critical intracellular signalling pathways, such [...] Read more.

Seaweed-derived bioactive compounds are regularly employed to treat human diseases. Sulfated polysaccharides are potent chemotherapeutic or chemopreventive medications since it has been discovered. They have exhibited anti-cancer properties by enhancing immunity and driving apoptosis. Through dynamic modulation of critical intracellular signalling pathways, such as control of ROS generation and preservation of essential cell survival and death processes, sulfated polysaccharides’ antioxidant and immunomodulatory potentials contribute to their disease-preventive effectiveness. Sulfated polysaccharides provide low cytotoxicity and good efficacy therapeutic outcomes via dynamic modulation of apoptosis in cancer. Understanding how sulfated polysaccharides affect human cancer cells and their molecular involvement in cell death pathways will showcase a new way of chemoprevention. In this review, the significance of apoptosis and autophagy-modulating sulfated polysaccharides has been emphasized, as well as the future direction of enhanced nano-formulation for greater clinical efficacy. Moreover, this review focuses on the recent findings about the possible mechanisms of chemotherapeutic use of sulfated polysaccharides, their potential as anti-cancer drugs, and proposed mechanisms of action to drive apoptosis in diverse malignancies. Because of their unique physicochemical and biological properties, sulfated polysaccharides are ideal for their bioactive ingredients, which can improve function and application in disease. However, there is a gap in the literature regarding the physicochemical properties and functionalities of sulfated polysaccharides and the use of sulfated polysaccharide-based delivery systems in functional cancer. Furthermore, the preclinical and clinical trials will reveal the drug’s efficacy in cancer. Full article

(This article belongs to the Special Issue Advances in Anticancer Drugs and Pharmacotherapy of Cancer)

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45 pages, 4011 KiB

Open AccessReview

Multifaceted Pharmacological Potentials of Curcumin, Genistein, and Tanshinone IIA through Proteomic Approaches: An In-Depth Review

by Farheen Badrealam Khan, Parul Singh, Yahya F. Jamous, Syed Azmal Ali, Abdullah, Shahab Uddin, Qamar Zia, Manoj Kumar Jena, Mohsina Khan, Mohammad Owais, Chih Yang Huang, Venkatesh Chanukuppa, Chrismawan Ardianto, Long Chiau Ming, Waqas Alam, Haroon Khan and Mohammad Akli Ayoub

Cancers 2023, 15(1), 249; https://doi.org/10.3390/cancers15010249 - 30 Dec 2022

Cited by 10 | Viewed by 4993

Abstract

Phytochemicals possess various intriguing pharmacological properties against diverse pathological conditions. Extensive studies are on-going to understand the structural/functional properties of phytochemicals as well as the molecular mechanisms of their therapeutic function against various disease conditions. Phytochemicals such as curcumin (Cur), genistein (Gen), and [...] Read more.

Phytochemicals possess various intriguing pharmacological properties against diverse pathological conditions. Extensive studies are on-going to understand the structural/functional properties of phytochemicals as well as the molecular mechanisms of their therapeutic function against various disease conditions. Phytochemicals such as curcumin (Cur), genistein (Gen), and tanshinone-IIA (Tan IIA) have multifaceted therapeutic potentials and various efforts are in progress to understand the molecular dynamics of their function with different tools and technologies. Cur is an active lipophilic polyphenol with pleiotropic function, and it has been shown to possess various intriguing properties including antioxidant, anti-inflammatory, anti-microbial, anticancer, and anti-genotoxic properties besides others beneficial properties. Similarly, Gen (an isoflavone) exhibits a wide range of vital functions including antioxidant, anti-inflammatory, pro-apoptotic, anti-proliferative, anti-angiogenic activities etc. In addition, Tan IIA, a lipophilic compound, possesses antioxidant, anti-angiogenic, anti-inflammatory, anticancer activities, and so on. Over the last few decades, the field of proteomics has garnered great momentum mainly attributed to the recent advancement in mass spectrometry (MS) techniques. It is envisaged that the proteomics technology has considerably contributed to the biomedical research endeavors lately. Interestingly, they have also been explored as a reliable approach to understand the molecular intricacies related to phytochemical-based therapeutic interventions. The present review provides an overview of the proteomics studies performed to unravel the underlying molecular intricacies of various phytochemicals such as Cur, Gen, and Tan IIA. This in-depth study will help the researchers in better understanding of the pharmacological potential of the phytochemicals at the proteomics level. Certainly, this review will be highly instrumental in catalyzing the translational shift from phytochemical-based biomedical research to clinical practice in the near future. Full article

(This article belongs to the Special Issue Advances in Anticancer Drugs and Pharmacotherapy of Cancer)

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41 pages, 1081 KiB

Open AccessReview

Targeting mTOR as a Cancer Therapy: Recent Advances in Natural Bioactive Compounds and Immunotherapy

by Abdelhakim Bouyahya, Aicha El Allam, Sara Aboulaghras, Saad Bakrim, Naoual El Menyiy, Mohammed Merae Alshahrani, Ahmed Abdullah Al Awadh, Taoufiq Benali, Learn-Han Lee, Nasreddine El Omari, Khang Wen Goh, Long Chiau Ming and Mohammad S. Mubarak

Cancers 2022, 14(22), 5520; https://doi.org/10.3390/cancers14225520 - 10 Nov 2022

Cited by 21 | Viewed by 6079

Abstract

The mammalian target of rapamycin (mTOR) is a highly conserved serine/threonine-protein kinase, which regulates many biological processes related to metabolism, cancer, immune function, and aging. It is an essential protein kinase that belongs to the phosphoinositide-3-kinase (PI3K) family and has two known signaling [...] Read more.

The mammalian target of rapamycin (mTOR) is a highly conserved serine/threonine-protein kinase, which regulates many biological processes related to metabolism, cancer, immune function, and aging. It is an essential protein kinase that belongs to the phosphoinositide-3-kinase (PI3K) family and has two known signaling complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). Even though mTOR signaling plays a critical role in promoting mitochondria-related protein synthesis, suppressing the catabolic process of autophagy, contributing to lipid metabolism, engaging in ribosome formation, and acting as a critical regulator of mRNA translation, it remains one of the significant signaling systems involved in the tumor process, particularly in apoptosis, cell cycle, and cancer cell proliferation. Therefore, the mTOR signaling system could be suggested as a cancer biomarker, and its targeting is important in anti-tumor therapy research. Indeed, its dysregulation is involved in different types of cancers such as colon, neck, cervical, head, lung, breast, reproductive, and bone cancers, as well as nasopharyngeal carcinoma. Moreover, recent investigations showed that targeting mTOR could be considered as cancer therapy. Accordingly, this review presents an overview of recent developments associated with the mTOR signaling pathway and its molecular involvement in various human cancer types. It also summarizes the research progress of different mTOR inhibitors, including natural and synthetised compounds and their main mechanisms, as well as the rational combinations with immunotherapies. Full article

(This article belongs to the Special Issue Advances in Anticancer Drugs and Pharmacotherapy of Cancer)

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18 pages, 674 KiB

Open AccessSystematic Review

Role of Immunotherapy in the Treatment of Cancer: A Systematic Review

by Sia Pei Ling, Long Chiau Ming, Jagjit Singh Dhaliwal, Madhu Gupta, Chrismawan Ardianto, Khang Wen Goh, Zahid Hussain and Naeem Shafqat

Cancers 2022, 14(21), 5205; https://doi.org/10.3390/cancers14215205 - 24 Oct 2022

Cited by 11 | Viewed by 7786

Abstract

Tremendous progress has been made in cancer research over the years, and, as a result, immunotherapy has emerged as an important therapy for the treatment of cancer, either as a stand-alone treatment or in conjunction with other cancer therapies. Immunotherapy has demonstrated encouraging [...] Read more.

Tremendous progress has been made in cancer research over the years, and, as a result, immunotherapy has emerged as an important therapy for the treatment of cancer, either as a stand-alone treatment or in conjunction with other cancer therapies. Immunotherapy has demonstrated encouraging outcomes and offers a viable strategy for not only enhancing the quality of life but also dramatically boosting the overall survival rate of cancer patients. The objective of this systematic review was to assess the efficacy of immunotherapy in the treatment of cancer. Databases such as PubMed and Science Direct were searched from their inception until September 2021, using the following keywords: cancer immunotherapy, cancer recurrence, cancer treatment options, and cancer therapies. The systematic review was conducted in accordance with the PRISMA protocol. There were a total of 599 articles; however, after applying the inclusion and exclusion criteria, the final review ended up with 34 publications. In conclusion, the studies have demonstrated that immunotherapy is a viable alternative treatment option for patients with recurrent or metastatic cancer, since the overall survival rate and progression-free survival rate were shown to be successful. Full article

(This article belongs to the Special Issue Advances in Anticancer Drugs and Pharmacotherapy of Cancer)

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