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Recent Advances in Anti-Cancer Drugs
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Recent Advances in Anti-Cancer Drugs

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 20 January 2025 | Viewed by 11111

Special Issue Editor

Dr. Christiana Neophytou

E-Mail Website
Guest Editor
Apoptosis and Cancer Chemoresistance Laboratory, Basic and Translational Cancer Research Center, Department of Life Sciences, European University Cyprus, Nicosia 2404, Cyprus
Interests: targeted cancer therapy; apoptosis; metastasis; cancer chemoresistance; pancreatic cancer; breast cancer; lung cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

It is a pleasure for me to invite you to contribute to this Special Issue in IJMS that aims to collect the latest information on a wide variety of novel anti-cancer therapies. Despite all the advances of the last decades, many challenges remain to target aggressive and resistant cancer. The design of new drugs or improvement of current therapies, remains at the forefront of cancer research. In addition, identifying the underlying causes of cancer chemoresistance as well as the discovery of biomarkers that predict patient response to treatment, are pivotal for enhancing therapeutic efficacy.

This Special issue aims at reporting the latest developments on anti-cancer therapy, with special emphasis on targeting difficult to treat cancers, including but not limited to triple negative breast cancer, lung, pancreatic cancer and glioblastoma. Efforts to evaluate the efficacy of anti-cancer drugs and reverse chemoresistance in the pre-clinical setting will also be included. Potential contributors are invited to submit papers on the following topics:

  • Synergistic anti-cancer therapy, especially involving small molecule inhibitors and agents derived from natural sources
  • Therapeutic approaches to reverse cancer chemoresistance as well as identification of underlying mechanisms of resistance
  • Recent developments in immunotherapy
  • Predictive biomarkers, especially derived from liquid biopsies, to determine therapeutic efficacy
  • Anti-cancer drugs targeting metastatic dormancy
  • Agents that modulate the tumor microenvironment for improving therapeutic efficacy
  • Modern approaches in preclinical drug discovery including 3D culture systems

Experimental studies in in vitro and in vivo models and review articles, are all welcome for consideration.

Dr. Christiana M. Neophytou
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • combination therapy in cancer
  • small molecule inhibitors in cancer
  • anti-cancer agents derived from natural sources
  • immunotherapy advances in cancer therapy
  • targeting metastatic dormancy
  • modulation of the tumor microenvironment
  • 3D model approaches in cancer research
  • predictive biomarkers for cancer chemoresistance

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Published Papers (5 papers)

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Research

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23 pages, 3045 KiB  
Article
Oleanolic Acid Dimers with Potential Application in Medicine—Design, Synthesis, Physico-Chemical Characteristics, Cytotoxic and Antioxidant Activity
by Andrzej Günther, Przemysław Zalewski, Szymon Sip, Piotr Ruszkowski and Barbara Bednarczyk-Cwynar
Int. J. Mol. Sci. 2024, 25(13), 6989; https://doi.org/10.3390/ijms25136989 - 26 Jun 2024
Cited by 2 | Viewed by 2299
Abstract
The present work aimed to obtain a set of oleanolic acid derivatives with a high level of cytotoxic and antioxidant activities and a low level of toxicity by applying an economical method. Oleanolic acid was alkylated with α,ω-dihalogenoalkane/α,ω-dihalogenoalkene to obtain 14 derivatives of [...] Read more.
The present work aimed to obtain a set of oleanolic acid derivatives with a high level of cytotoxic and antioxidant activities and a low level of toxicity by applying an economical method. Oleanolic acid was alkylated with α,ω-dihalogenoalkane/α,ω-dihalogenoalkene to obtain 14 derivatives of dimer structure. All of the newly obtained compounds were subjected to QSAR computational analysis to evaluate the probability of the occurrence of different types of pharmacological activities depending on the structure of the analysed compound. All dimers were tested for cytotoxicity activity and antioxidant potential. The cytotoxicity was tested on the SKBR-3, SKOV-3, PC-3, and U-87 cancer cell lines with the application of the MTT assay. The HDF cell line was applied to evaluate the tested compounds’ Selectivity Index. The antioxidant test was performed with a DPPH assay. Almost all triterpene dimers showed a high level of cytotoxic activity towards selected cancer cell lines, with an IC50 value below 10 µM. The synthesised derivatives of oleanolic acid exhibited varying degrees of antioxidant activity, surpassing that of the natural compound in several instances. Employing the DPPH assay, compounds 2a, 2b, and 2f emerged as promising candidates, demonstrating significantly higher Trolox equivalents and highlighting their potential for pharmaceutical and nutraceutical applications. Joining two oleanolic acid residues through their C-17 carboxyl group using α,ω-dihalogenoalkanes/α,ω-dihalogenoalkenes resulted in the synthesis of highly potent cytotoxic agents with favourable SIs and high levels of antioxidant activity. Full article
(This article belongs to the Special Issue Recent Advances in Anti-Cancer Drugs)
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13 pages, 4229 KiB  
Article
Preclinical Evaluation of Biodistribution and Toxicity of [211At]PSMA-5 in Mice and Primates for the Targeted Alpha Therapy against Prostate Cancer
by Tadashi Watabe, Kazuko Kaneda-Nakashima, Yuichiro Kadonaga, Kazuhiro Ooe, Thosapol Sampunta, Naoki Hirose, Xiaojie Yin, Hiromitsu Haba, Yukiyoshi Kon, Atsushi Toyoshima, Jens Cardinale, Frederik L. Giesel, Koichi Fukase, Noriyuki Tomiyama and Yoshifumi Shirakami
Int. J. Mol. Sci. 2024, 25(11), 5667; https://doi.org/10.3390/ijms25115667 - 23 May 2024
Viewed by 1721
Abstract
Astatine (211At) is a cyclotron-produced alpha emitter with a physical half-life of 7.2 h. In our previous study, the 211At-labeled prostate-specific membrane antigen (PSMA) compound ([211At]PSMA-5) exhibited excellent tumor growth suppression in a xenograft model. We conducted preclinical [...] Read more.
Astatine (211At) is a cyclotron-produced alpha emitter with a physical half-life of 7.2 h. In our previous study, the 211At-labeled prostate-specific membrane antigen (PSMA) compound ([211At]PSMA-5) exhibited excellent tumor growth suppression in a xenograft model. We conducted preclinical biodistribution and toxicity studies for the first-in-human clinical trial. [211At]PSMA-5 was administered to both normal male ICR mice (n = 85) and cynomolgus monkeys (n = 2). The mice were divided into four groups for the toxicity study: 5 MBq/kg, 12 MBq/kg, 35 MBq/kg, and vehicle control, with follow-ups at 1 day (n = 10 per group) and 14 days (n = 5 per group). Monkeys were observed 24 h post-administration of [211At]PSMA-5 (9 MBq/kg). Blood tests and histopathological examinations were performed at the end of the observation period. Blood tests in mice indicated no significant myelosuppression or renal dysfunction. However, the monkeys displayed mild leukopenia 24 h post-administration. Despite the high accumulation in the kidneys and thyroid, histological analysis revealed no abnormalities. On day 1, dose-dependent single-cell necrosis/apoptosis was observed in the salivary glands of mice and intestinal tracts of both mice and monkeys. Additionally, tingible body macrophages in the spleen and lymph nodes indicated phagocytosis of apoptotic B lymphocytes. Cortical lymphopenia (2/10) in the thymus and a decrease in the bone marrow cells (9/10) were observed in the 35 MBq/kg group in mice. These changes were transient, with no irreversible toxicity observed in mice 14 days post-administration. This study identified no severe toxicities associated with [211At]PSMA-5, highlighting its potential as a next-generation targeted alpha therapy for prostate cancer. The sustainable production of 211At using a cyclotron supports its applicability for clinical use. Full article
(This article belongs to the Special Issue Recent Advances in Anti-Cancer Drugs)
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21 pages, 4795 KiB  
Article
Silver Complexes of Miconazole and Metronidazole: Potential Candidates for Melanoma Treatment
by Małgorzata Fabijańska, Agnieszka J. Rybarczyk-Pirek, Justyna Dominikowska, Karolina Stryjska, Dominik Żyro, Magdalena Markowicz-Piasecka, Małgorzata Iwona Szynkowska-Jóźwik, Justyn Ochocki and Joanna Sikora
Int. J. Mol. Sci. 2024, 25(10), 5081; https://doi.org/10.3390/ijms25105081 - 7 May 2024
Cited by 1 | Viewed by 1295
Abstract
Melanoma, arguably the deadliest form of skin cancer, is responsible for the majority of skin-cancer-related fatalities. Innovative strategies concentrate on new therapies that avoid the undesirable effects of pharmacological or medical treatment. This article discusses the chemical structures of [(MTZ)2AgNO3 [...] Read more.
Melanoma, arguably the deadliest form of skin cancer, is responsible for the majority of skin-cancer-related fatalities. Innovative strategies concentrate on new therapies that avoid the undesirable effects of pharmacological or medical treatment. This article discusses the chemical structures of [(MTZ)2AgNO3], [(MTZ)2Ag]2SO4, [Ag(MCZ)2NO3], [Ag(MCZ)2BF4], [Ag(MCZ)2SbF6] and [Ag(MCZ)2ClO4] (MTZ—metronidazole; MCZ—miconazole) silver(I) compounds and the possible relationship between the molecules and their cytostatic activity against melanoma cells. Molecular Hirshfeld surface analysis and computational methods were used to examine the possible association between the structure and anticancer activity of the silver(I) complexes and compare the cytotoxicity of the silver(I) complexes of metronidazole and miconazole with that of silver(I) nitrate, cisplatin, metronidazole and miconazole complexes against A375 and BJ cells. Additionally, these preliminary biological studies found the greatest IC50 values against the A375 line were demonstrated by [Ag(MCZ)2NO3] and [(MTZ)2AgNO3]. The compound [(MTZ)2AgNO3] was three-fold more toxic to the A375 cells than the reference (cisplatin) and 15 times more cytotoxic against the A375 cells than the normal BJ cells. Complexes of metronidazole with Ag(I) are considered biocompatible at a concentration below 50 µmol/L. Full article
(This article belongs to the Special Issue Recent Advances in Anti-Cancer Drugs)
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Review

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27 pages, 896 KiB  
Review
The Role of Tumor Microenvironment in Pancreatic Cancer Immunotherapy: Current Status and Future Perspectives
by Fotini Poyia, Christiana M. Neophytou, Maria-Ioanna Christodoulou and Panagiotis Papageorgis
Int. J. Mol. Sci. 2024, 25(17), 9555; https://doi.org/10.3390/ijms25179555 - 3 Sep 2024
Viewed by 1732
Abstract
Pancreatic cancer comprises different subtypes, where most cases include ductal adenocarcinoma (PDAC). It is one of the deadliest tumor types, with a poor prognosis. In the majority of patients, the disease has already spread by the time of diagnosis, making full recovery unlikely [...] Read more.
Pancreatic cancer comprises different subtypes, where most cases include ductal adenocarcinoma (PDAC). It is one of the deadliest tumor types, with a poor prognosis. In the majority of patients, the disease has already spread by the time of diagnosis, making full recovery unlikely and increasing mortality risk. Despite developments in its detection and management, including chemotherapy, radiotherapy, and targeted therapies as well as advances in immunotherapy, only in about 13% of PDAC patients does the overall survival exceed 5 years. This may be attributed, at least in part, to the highly desmoplastic tumor microenvironment (TME) that acts as a barrier limiting perfusion, drug delivery, and immune cell infiltration and contributes to the establishment of immunologically ‘cold’ conditions. Therefore, there is an urgent need to unravel the complexity of the TME that promotes PDAC progression and decipher the mechanisms of pancreatic tumors’ resistance to immunotherapy. In this review, we provide an overview of the major cellular and non-cellular components of PDAC TME, as well as their biological interplays. We also discuss the current state of PDAC therapeutic treatments and focus on ongoing and future immunotherapy efforts and multimodal treatments aiming at remodeling the TME to improve therapeutic efficacy. Full article
(This article belongs to the Special Issue Recent Advances in Anti-Cancer Drugs)
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20 pages, 1523 KiB  
Review
Prognostic Value of Monocarboxylate Transporter 1 Overexpression in Cancer: A Systematic Review
by Ana Silva, Mónica Costa Cerqueira, Beatriz Rosa, Catarina Sobral, Filipa Pinto-Ribeiro, Marta Freitas Costa, Fátima Baltazar and Julieta Afonso
Int. J. Mol. Sci. 2023, 24(6), 5141; https://doi.org/10.3390/ijms24065141 - 7 Mar 2023
Cited by 11 | Viewed by 2849
Abstract
Energy production by cancer is driven by accelerated glycolysis, independently of oxygen levels, which results in increased lactate production. Lactate is shuttled to and from cancer cells via monocarboxylate transporters (MCTs). MCT1 works both as an importer and an extruder of lactate, being [...] Read more.
Energy production by cancer is driven by accelerated glycolysis, independently of oxygen levels, which results in increased lactate production. Lactate is shuttled to and from cancer cells via monocarboxylate transporters (MCTs). MCT1 works both as an importer and an extruder of lactate, being widely studied in recent years and generally associated with a cancer aggressiveness phenotype. The aim of this systematic review was to assess the prognostic value of MCT1 immunoexpression in different malignancies. Study collection was performed by searching nine different databases (PubMed, EMBASE, ScienceDirect, Scopus, Cochrane Library, Web of Science, OVID, TRIP and PsycINFO), using the keywords “cancer”, “Monocarboxylate transporter 1”, “SLC16A1” and “prognosis”. Results showed that MCT1 is an indicator of poor prognosis and decreased survival for cancer patients in sixteen types of malignancies; associations between the transporter’s overexpression and larger tumour sizes, higher disease stage/grade and metastasis occurrence were also frequently observed. Yet, MCT1 overexpression correlated with better outcomes in colorectal cancer, pancreatic ductal adenocarcinoma and non-small cell lung cancer patients. These results support the applicability of MCT1 as a biomarker of prognosis, although larger cohorts would be necessary to validate the overall role of MCT1 as an outcome predictor. Full article
(This article belongs to the Special Issue Recent Advances in Anti-Cancer Drugs)
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