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Biomarkers and New Therapeutical Strategies for Cancer Diagnosis and Treatment

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 49032

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Special Issue Editors

Prof. Dr. Agata Grazia D'Amico

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Department of Drug and Health Sciences, University of Catania, 95100 Catania, Italy
Interests: neuroanatomy; neuroscience; neuropeptides; neural stem cells; identification of carcinogenic bi-omarkers; study of molecular mechanisms involved in cancers progression
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Luca Vanella

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Department of Drug and Health Sciences, Section of Biochemistry, University of Catania, Catania, Italy
Interests: biochemistry; antioxidants; oxidative stress; heme oxygenase
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Dr. Antonella Marino Gammazza

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Guest Editor

Department of Biomedicine, Neuroscience and Advanced Diagnostics Institute of Human Anatomy and Histology, University of Palermo, Palermo, Italy
Interests: anatomy; oxidative stress; molecular chaperones; cell signaling; cell biology; bioinformatics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cancers could be considered multigenic pathologies with complex etiologies. Many tumors are characterized by high histological and molecular heterogeneity as well as highly tumorigenic subpopulation of cancerous stem cells derived from normal stem cells affected by the inflammatory microenvironment.

These pluripotent stem cells are the main culprits of tumor resistance to chemotherapy. Today, there are many antineoplastic agents used in clinical practice that have developed severe side effects and are also responsible for the alteration of molecular mechanisms leading to drug resistance. Therefore, identification of new therapeutical targets and the characterization of molecular mechanisms underlying cancer progression and chemoresistance represent an emerging issue in the oncology field.

Notably, a growing number of studies have indicated that miRNAs have multiple functions in tumorigenesis, cancer cell proliferation and apoptosis, cancer cell invasion and migration, therapeutic resistance, and the tumor microenvironment.

The aim of this Special Issue is to gather information about promising biomarkers useful for diagnosis and patient monitoring in different cancers, as well as the identification of bioactive compounds to be used as therapeutic agents to counteract proliferation and chemoresistance. The latter is often associated with the overexpression of endogenous antioxidant systems and alteration of redox homeostasis. Preclinical studies can be designed to transfer new knowledge from basic to biomedical science, in order to generate advanced diagnostic and therapeutic applications.

Prof. Agata Grazia D'Amico
Prof. Luca Vanella
Prof. Antonella Marino Gammazza
Guest Editors

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Keywords

cancer
biomarkers
neuropeptides
bioactive compounds
cell signaling
target therapy

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Published Papers (10 papers)

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Research

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13 pages, 2540 KiB

Open AccessArticle

Combined Evaluation of MAP1LC3B and SQSTM1 for Biological and Clinical Significance in Ductal Carcinoma of Breast Cancer

by Pei-Feng Liu, Chih-Wen Shu, Hsiu-Chen Yang, Cheng-Hsin Lee, Huei-Han Liou, Luo-Ping Ger, Yen-Dun Tony Tzeng and Wen-Ching Wang

Biomedicines 2021, 9(11), 1514; https://doi.org/10.3390/biomedicines9111514 - 21 Oct 2021

Cited by 2 | Viewed by 2168

Abstract

Breast cancer is the leading cause of cancer death in women worldwide. The microtubule-associated protein light chain 3B (MAP1LC3B) and adaptor sequestosome 1 (SQSTM1) are two major markers for autophagy. Increased protein levels of MAP1LC3B and SQSTM1 are considered to be causes of autophagy inhibition or activation in various types of cancers. However, the roles of MAP1LC3B and SQSTM1 in breast cancer are still not clear. Using a tissue microarray from 274 breast invasive ductal carcinoma (IDC) patients, we found that tumor tissues showed higher protein levels of MAP1LC3B and cytoplasmic SQSTM1 in comparison to those in adjacent normal tissues. Moreover, high levels of MAP1LC3B were associated with better survival, including disease-specific survival and disease-free survival (DFS) in IDC patients. Furthermore, high co-expression of MAP1LC3B and SQSTM1 was significantly associated with better DFS in IDC patients. Astonishingly, the autophagy inhibitor accumulated the protein levels of MAP1LC3B/SQSTM1 and enhanced the cytotoxic effects of cisplatin and paclitaxel in MCF7 and BT474 breast cancer cell lines, implying that autophagy inhibition might result in poor prognosis and chemosensitivity in IDC. Taken together, high co-expression of MAP1LC3B and SQSTM1 might serve as a potential diagnostic and prognostic biomarker for IDC patients. Full article

(This article belongs to the Special Issue Biomarkers and New Therapeutical Strategies for Cancer Diagnosis and Treatment)

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15 pages, 6438 KiB

Open AccessArticle

Multi-Omics Reveals the Immunological Role and Prognostic Potential of Mitochondrial Ubiquitin Ligase MARCH5 in Human Breast Cancer

by Pei-Yi Chu, Yen-Dun Tony Tzeng, Yi-Han Chiu, Hung-Yu Lin, Chen-Hsin Kuo, Ming-Feng Hou and Chia-Jung Li

Biomedicines 2021, 9(10), 1329; https://doi.org/10.3390/biomedicines9101329 - 26 Sep 2021

Cited by 12 | Viewed by 3004

Abstract

E3 ubiquitin-linked enzyme MARCH5, also known as membrane-associated circular finger 5, is an enzyme encoded by the human MARCH5 gene. The main objective of this study was to visualize the prognosis of MARCH5 in breast cancer and to determine the relationship between MARCH5 expression and tumor immunity. MARCH5 expression was significantly higher in several cancers, including breast cancer (BRCA), compared with corresponding normal tissues. Not only was high MARCH5 expression associated with poorer overall survival, but also MARCH5 expression was positively correlated with the number of tumor-infiltrating immune cells in BRCA malignant tissues. Furthermore, MARCH5 expression showed a strong correlation with various immune markers of BRCA, suggesting its role in regulating tumor immunity. MARCH5 is a useful prognostic biomarker in several cancers, and its expression is highly correlated with tumor immune cell infiltration, and increased MARCH5 expression may serve as a new biomarker for BRCA diagnosis and prognosis. Full article

(This article belongs to the Special Issue Biomarkers and New Therapeutical Strategies for Cancer Diagnosis and Treatment)

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18 pages, 4574 KiB

Open AccessArticle

Effect of PACAP on Hypoxia-Induced Angiogenesis and Epithelial–Mesenchymal Transition in Glioblastoma

by Grazia Maugeri, Agata Grazia D’Amico, Salvatore Saccone, Concetta Federico, Daniela Maria Rasà, Rosario Caltabiano, Giuseppe Broggi, Salvatore Giunta, Giuseppe Musumeci and Velia D’Agata

Biomedicines 2021, 9(8), 965; https://doi.org/10.3390/biomedicines9080965 - 5 Aug 2021

Cited by 17 | Viewed by 2866

Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) exerts different effects in various human cancer. In glioblastoma (GBM), PACAP has been shown to interfere with the hypoxic micro-environment through the modulation of hypoxia-inducible factors via PI3K/AKT and MAPK/ERK pathways inhibition. Considering that hypoxic tumor micro-environment is strictly linked to angiogenesis and Epithelial–Mesenchymal transition (EMT), in the present study, we have investigated the ability of PACAP to regulate these events. Results have demonstrated that PACAP and its related receptor, PAC1R, are expressed in hypoxic area of human GBM colocalizing either in epithelial or mesenchymal cells. By using an in vitro model of GBM cells, we have observed that PACAP interferes with hypoxic/angiogenic pathway by reducing vascular-endothelial growth factor (VEGF) release and inhibiting formation of vessel-like structures in H5V endothelial cells cultured with GBM-conditioned medium. Moreover, PACAP treatment decreased the expression of mesenchymal markers such as vimentin, matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) as well as CD44 in GBM cells by affecting their invasiveness. In conclusion, our study provides new insights regarding the multimodal role of PACAP in GBM malignancy. Full article

(This article belongs to the Special Issue Biomarkers and New Therapeutical Strategies for Cancer Diagnosis and Treatment)

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Review

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25 pages, 2808 KiB

Open AccessReview

Parthenolide and Its Soluble Analogues: Multitasking Compounds with Antitumor Properties

by Daniela Carlisi, Marianna Lauricella, Antonella D’Anneo, Anna De Blasio, Adriana Celesia, Giovanni Pratelli, Antonietta Notaro, Giuseppe Calvaruso, Michela Giuliano and Sonia Emanuele

Biomedicines 2022, 10(2), 514; https://doi.org/10.3390/biomedicines10020514 - 21 Feb 2022

Cited by 24 | Viewed by 4302

Abstract

Due to its chemical properties and multiple molecular effects on different tumor cell types, the sesquiterpene lactone parthenolide (PN) can be considered an effective drug with significant potential in cancer therapy. PN has been shown to induce either classic apoptosis or alternative caspase-independent forms of cell death in many tumor models. The therapeutical potential of PN has been increased by chemical design and synthesis of more soluble analogues including dimethylaminoparthenolide (DMAPT). This review focuses on the molecular mechanisms of both PN and analogues action in tumor models, highlighting their effects on gene expression, signal transduction and execution of different types of cell death. Recent findings indicate that these compounds not only inhibit prosurvival transcriptional factors such as NF-κB and STATs but can also determine the activation of specific death pathways, increasing intracellular reactive oxygen species (ROS) production and modifications of Bcl-2 family members. An intriguing property of these compounds is its specific targeting of cancer stem cells. The unusual actions of PN and its analogues make these agents good candidates for molecular targeted cancer therapy. Full article

(This article belongs to the Special Issue Biomarkers and New Therapeutical Strategies for Cancer Diagnosis and Treatment)

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18 pages, 2793 KiB

Open AccessReview

RETRACTED: Animal Models in Bladder Cancer

by Traian Constantin, Mihai Păvălean, Ștefana Bucur, Maria Magdalena Constantin, Alin Codruț Nicolescu, Irina Pacu and Victor Mădan

Biomedicines 2021, 9(12), 1762; https://doi.org/10.3390/biomedicines9121762 - 24 Nov 2021

Cited by 5 | Viewed by 4266 | Retraction

Abstract

Background: Bladder cancer (urothelial cancer of the bladder) is the most common malignancy affecting the urinary system with an increasing incidence and mortality. Mouse models of bladder cancer should possess a high value of reproducibility, predictability, and translatability to allow mechanistic, chemo-preventive, and therapeutic studies that can be furthered into human clinical trials. Objectives: To provide an overview and resources on the origin, molecular and pathological characteristics of commonly used animal models in bladder cancer. Methods: A PubMed and Web of Science search was performed for relevant articles published between 1980 and 2021 using words such as: “bladder” and/or “urothelial carcinoma” and animal models. Animal models of bladder cancer can be categorized as autochthonous (spontaneous) and non-autochthonous (transplantable). The first are either chemically induced models or genetically engineered models. The transplantable models can be further subclassified as syngeneic (murine bladder cancer cells implanted into immunocompetent or transgenic mice) and xenografts (human bladder cancer cells implanted into immune-deficient mice). These models can be further divided—based on the site of the tumor—as orthotopic (tumor growth occurs within the bladder) and heterotopic (tumor growth occurs outside of the bladder). Full article

(This article belongs to the Special Issue Biomarkers and New Therapeutical Strategies for Cancer Diagnosis and Treatment)

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25 pages, 3193 KiB

Open AccessReview

Role of PARP in TNBC: Mechanism of Inhibition, Clinical Applications, and Resistance

by Desh Deepak Singh, Amna Parveen and Dharmendra Kumar Yadav

Biomedicines 2021, 9(11), 1512; https://doi.org/10.3390/biomedicines9111512 - 21 Oct 2021

Cited by 31 | Viewed by 8825

Abstract

Triple-negative breast cancer is a combative cancer type with a highly inflated histological grade that leads to poor theragnostic value. Gene, protein, and receptor-specific targets have shown effective clinical outcomes in patients with TNBC. Cells are frequently exposed to DNA-damaging agents. DNA damage is repaired by multiple pathways; accumulations of mutations occur due to damage to one or more pathways and lead to alterations in normal cellular mechanisms, which lead to development of tumors. Advances in target-specific cancer therapies have shown significant momentum; most treatment options cause off-target toxicity and side effects on healthy tissues. PARP (poly(ADP-ribose) polymerase) is a major protein and is involved in DNA repair pathways, base excision repair (BER) mechanisms, homologous recombination (HR), and nonhomologous end-joining (NEJ) deficiency-based repair mechanisms. DNA damage repair deficits cause an increased risk of tumor formation. Inhibitors of PARP favorably kill cancer cells in BRCA-mutations. For a few years, PARPi has shown promising activity as a chemotherapeutic agent in BRCA1- or BRCA2-associated breast cancers, and in combination with chemotherapy in triple-negative breast cancer. This review covers the current results of clinical trials testing and future directions for the field of PARP inhibitor development. Full article

(This article belongs to the Special Issue Biomarkers and New Therapeutical Strategies for Cancer Diagnosis and Treatment)

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32 pages, 5701 KiB

Open AccessReview

Therapeutic Potential of PARP Inhibitors in the Treatment of Gastrointestinal Cancers

by Abdullah Alhusaini, Aoife Cannon, Stephen G. Maher, John V. Reynolds and Niamh Lynam-Lennon

Biomedicines 2021, 9(8), 1024; https://doi.org/10.3390/biomedicines9081024 - 16 Aug 2021

Cited by 13 | Viewed by 4867

Abstract

Gastrointestinal (GI) malignancies are a major global health burden, with high mortality rates. The identification of novel therapeutic strategies is crucial to improve treatment and survival of patients. The poly (ADP-ribose) polymerase (PARP) enzymes involved in the DNA damage response (DDR) play major roles in the development, progression and treatment response of cancer, with PARP inhibitors (PARPi) currently used in the clinic for breast, ovarian, fallopian, primary peritoneal, pancreatic and prostate cancers with deficiencies in homologous recombination (HR) DNA repair. This article examines the current evidence for the role of the DDR PARP enzymes (PARP1, 2, 3 and 4) in the development, progression and treatment response of GI cancers. Furthermore, we discuss the role of HR status as a predictive biomarker of PARPi efficacy in GI cancer patients and examine the pre-clinical and clinical evidence for PARPi and cytotoxic therapy combination strategies in GI cancer. We also include an analysis of the genomic and transcriptomic landscape of the DDR PARP genes and key HR genes (BRCA1, BRCA2, ATM, RAD51, MRE11, PALB2) in GI patient tumours (n = 1744) using publicly available datasets to identify patients that may benefit from PARPi therapeutic approaches. Full article

(This article belongs to the Special Issue Biomarkers and New Therapeutical Strategies for Cancer Diagnosis and Treatment)

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26 pages, 3728 KiB

Open AccessReview

TNBC: Potential Targeting of Multiple Receptors for a Therapeutic Breakthrough, Nanomedicine, and Immunotherapy

by Desh Deepak Singh and Dharmendra Kumar Yadav

Biomedicines 2021, 9(8), 876; https://doi.org/10.3390/biomedicines9080876 - 23 Jul 2021

Cited by 52 | Viewed by 11303

Abstract

Triple-negative breast cancer (TNBC) is a heterogeneous, recurring cancer associated with a high rate of metastasis, poor prognosis, and lack of therapeutic targets. Although target-based therapeutic options are approved for other cancers, only limited therapeutic options are available for TNBC. Cell signaling and receptor-specific targets are reportedly effective in patients with TNBC under specific clinical conditions. However, most of these cancers are unresponsive, and there is a requirement for more effective treatment modalities. Further, there is a lack of effective biomarkers that can distinguish TNBC from other BC subtypes. ER, PR, and HER2 help identify TNBC and are widely used to identify patients who are most likely to respond to diverse therapeutic strategies. In this review, we discuss the possible treatment options for TNBC based on its inherent subtype receptors and pathways, such as p53 signaling, AKT signaling, cell cycle regulation, DNA damage, and programmed cell death, which play essential roles at multiple stages of TNBC development. We focus on poly-ADP ribose polymerase 1, androgen receptor, vascular endothelial growth factor receptor, and epidermal growth factor receptor as well as the application of nanomedicine and immunotherapy in TNBC and discuss their potential applications in drug development for TNBC. Full article

(This article belongs to the Special Issue Biomarkers and New Therapeutical Strategies for Cancer Diagnosis and Treatment)

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Other

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15 pages, 1214 KiB

Open AccessSystematic Review

Investigating the Role of Circulating miRNAs as Biomarkers in Colorectal Cancer: An Epidemiological Systematic Review

by Lucia Dansero, Fulvio Ricceri, Laura De Marco, Valentina Fiano, Ginevra Nesi, Lisa Padroni, Lorenzo Milani, Saverio Caini, Giovanna Masala, Claudia Agnoli and Carlotta Sacerdote

Biomedicines 2022, 10(9), 2224; https://doi.org/10.3390/biomedicines10092224 - 8 Sep 2022

Cited by 7 | Viewed by 2080

Abstract

Colorectal cancer (CRC) is one of the most common cancers worldwide. Primary and secondary preventions are key to reducing the global burden. MicroRNAs (miRNAs) are a group of small non-coding RNA molecules, which seem to have a role either as tumor suppressor genes or oncogenes and to be related to cancer risk factors, such as obesity and inflammation. We conducted a systematic review and meta-analysis to identify circulating miRNAs related to CRC diagnosis that could be selected as biomarkers in a meet-in-the-middle analysis. Forty-four studies were included in the systematic review and nine studies in the meta-analysis. The pooled sensitivity and specificity of miR-21 for CRC diagnosis were 77% (95% CI: 69–84) and 82% (95% CI: 70–90), respectively, with an AUC of 0.86 (95% CI: 0.82–0.88). Several miRNAs were found to be dysregulated, distinguishing patients with CRC from healthy controls. However, little consistency was present across the included studies, making it challenging to identify specific miRNAs, which were consistently validated. Understanding the mechanisms by which miRNAs become biologically embedded in cancer initiation and promotion may help better understand cancer pathways to develop more effective prevention strategies and therapy approaches. Full article

(This article belongs to the Special Issue Biomarkers and New Therapeutical Strategies for Cancer Diagnosis and Treatment)

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39 pages, 1191 KiB

Open AccessSystematic Review

New Therapeutic Perspectives in the Treatment of Uveal Melanoma: A Systematic Review

by Mario Damiano Toro, Lucia Gozzo, Luciano Tracia, Marco Cicciù, Filippo Drago, Claudio Bucolo, Teresio Avitabile, Robert Rejdak, Katarzyna Nowomiejska, Sandrine Zweifel, Yacoub A. Yousef, Rashed Nazzal and Giovanni Luca Romano

Biomedicines 2021, 9(10), 1311; https://doi.org/10.3390/biomedicines9101311 - 24 Sep 2021

Cited by 26 | Viewed by 3641

Abstract

Uveal melanoma (UM) is a rare disease, but the most common primary intraocular cancer, mostly localized in the choroid. Currently, the first-line treatment options for UM are radiation therapy, resection, and enucleation. However, although these treatments could potentially be curative, half of all patients will develop metastatic disease, whose prognosis is still poor. Indeed, effective therapeutic options for patients with advanced or metastatic disease are still lacking. Recently, the development of new treatment modalities with a lower incidence of adverse events, a better disease control rate, and new therapeutic approaches, have merged as new potential and promising therapeutic strategies. Additionally, several clinical trials are ongoing to find new therapeutic options, mainly for those with metastatic disease. Many interventions are still in the preliminary phases of clinical development, being investigated in phase I trial or phase I/II. The success of these trials could be crucial for changing the prognosis of patients with advanced/metastatic UM. In this systematic review, we analyzed all emerging and available literature on the new perspectives in the treatment of UM and patient outcomes; furthermore, their current limitations and more common adverse events are summarized. Full article

(This article belongs to the Special Issue Biomarkers and New Therapeutical Strategies for Cancer Diagnosis and Treatment)

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