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Special Issue "New Strategies in Cancer Pharmacotherapy: Development of Hormonal Antineoplastic Drugs, Cytotoxic Drugs and Targeted Therapies"

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

Deadline for manuscript submissions: 30 November 2019.

Special Issue Editors

Guest Editor
Dr. Carlos Martínez-Campa Website E-Mail
Department of Physiology and Pharmacology, University of Cantabria, Santander, Spain
Interests: melatonin; breast cancer; chemotherapy; radiotherapy; apoptosis; angiogenesis; gene expression
Guest Editor
Dr. Carolina Alonso-González Website E-Mail
Department of Physiology and Pharmacology, University of Cantabria, Santander, Spain
Interests: melatonin and mammary cancer

Special Issue Information

Dear Colleagues,

Cancer is a group of diseases characterized by abnormal growth and proliferation of cells which, in most cases, forms a tumor. Primary tumor growth is often accompanied by angiogenesis, progression, and metastasis. Some cancers are hormone-independent, whilst others are responsive to hormones (principally, sexual hormones in breast, prostate, and ovary cancers). For both hormone-dependent and independent cancers, the effectiveness of cytotoxic drugs is limited, and their use is often accompanied by severe adverse effects, leading to the continuous search for “next-generation” compounds and/or delivery strategies. Over the past two decades, great effort has been made to develop new effective therapies. In the case of hormone-dependent cancers, hormone antagonists, inhibitors, and analogues are currently used. In addition, emerging knowledge about the molecular mechanisms involved in the generation and progression of tumors has led to the design of promising therapies against specific molecular targets. The combination of hormonal analogues, classic or new-generation cytotoxic drugs, and targeted therapies (small RNAs, monoclonal antibodies) with new forms of drug delivery will hopefully have future successful application in cancer treatment.

This Special Issue “New strategies in cancer pharmacotherapy: Development of hormonal antineoplastic drugs, cytotoxic drugs and targeted therapies” will include reviews and original research on advances in cancer treatment. Novel insights into the development and assay of new compounds either alone or in combination are of particular interest for this issue.

Dr. Carlos Martínez-Campa
Dr. Carolina Alonso-González
Guest Editors

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 papers will be 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

  • cancer treatment
  • hormone analogues
  • targeted therapy
  • chemotherapy
  • cytotoxic drugs
  • signaling pathways
  • gene expresión
  • angiogénesis
  • metastasis

Published Papers (3 papers)

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Research

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Open AccessArticle
Melatonin Modulation of Radiation and Chemotherapeutics-induced Changes on Differentiation of Breast Fibroblasts
Int. J. Mol. Sci. 2019, 20(16), 3935; https://doi.org/10.3390/ijms20163935 - 13 Aug 2019
Abstract
Melatonin exerts oncostatic actions and sensitizes tumor cells to chemotherapeutics or radiation. In our study, we investigated the effects of docetaxel, vinorelbine, and radiation on human breast fibroblasts and its modulation by melatonin. Docetaxel or vinorelbine inhibits proliferation and stimulates the differentiation of [...] Read more.
Melatonin exerts oncostatic actions and sensitizes tumor cells to chemotherapeutics or radiation. In our study, we investigated the effects of docetaxel, vinorelbine, and radiation on human breast fibroblasts and its modulation by melatonin. Docetaxel or vinorelbine inhibits proliferation and stimulates the differentiation of breast preadipocytes, by increasing C/EBPα and PPARγ expression and by downregulating tumor necrosis factor α (TNFα), interleukin 6 (IL-6), and IL-11 expression. Radiation inhibits both proliferation and differentiation through the downregulation of C/EBPα and PPARγ and by stimulating TNFα expression. In addition, docetaxel and radiation decrease aromatase activity and expression by decreasing aromatase promoter II and cyclooxygenases 1 and 2 (COX-1 and COX-2) expression. Melatonin potentiates the stimulatory effect of docetaxel and vinorelbine on differentiation and their inhibitory effects on aromatase activity and expression, by increasing the stimulatory effect on C/EBPα and PPARγ expression and the downregulation of antiadipogenic cytokines and COX expression. Melatonin also counteracts the inhibitory effect of radiation on differentiation of preadipocytes, by increasing C/EBPα and PPARγ expression and by decreasing TNFα expression. Melatonin also potentiates the inhibitory effect exerted by radiation on aromatase activity and expression by increasing the downregulation of promoter II, and COX-1 and COX-2 expression. Our findings suggest that melatonin modulates regulatory effects induced by chemotherapeutic drugs or radiation on preadipocytes, which makes it a promising adjuvant for chemotherapy and radiotherapy sensibilization. Full article
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Open AccessArticle
The Antitumor Activity of TCR-Mimic Antibody-Drug Conjugates (TCRm-ADCs) Targeting the Intracellular Wilms Tumor 1 (WT1) Oncoprotein
Int. J. Mol. Sci. 2019, 20(16), 3912; https://doi.org/10.3390/ijms20163912 - 12 Aug 2019
Abstract
Wilms tumor 1 (WT1) oncoprotein is an intracellular oncogenic transcription factor which is barely expressed in normal adult tissues but over expressed in a variety of leukemias and solid cancers. WT1-derived HLA-A*02:01 T cell epitope, RMFPNAPYL (RMF), is a validated target for T [...] Read more.
Wilms tumor 1 (WT1) oncoprotein is an intracellular oncogenic transcription factor which is barely expressed in normal adult tissues but over expressed in a variety of leukemias and solid cancers. WT1-derived HLA-A*02:01 T cell epitope, RMFPNAPYL (RMF), is a validated target for T cell-based immunotherapy. We generated two T cell receptor mimic antibody-drug conjugates (TCRm-ADCs), ESK-MMAE, and Q2L-MMAE, against WT1 RMF/HLA-A*02:01 complex with distinct affinities, which mediate specific antitumor activity. Although ESK-MMAE showed higher tumor growth inhibition ratio in vivo, the efficacy of them was not so promising, which might be due to low expression of peptide/HLA targets. Therefore, we explored a bispecific TCRm-ADC that exerted more potent tumor cytotoxicity compared with TCRm-ADCs. Hence, our findings validate the feasibility of the presenting intracellular peptides as the targets of ADCs, which broadens the antigen selection range of antibody-based drugs and provides new strategies for precision medicine in tumor therapy. Full article
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Review

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Open AccessReview
Phenformin as an Anticancer Agent: Challenges and Prospects
Int. J. Mol. Sci. 2019, 20(13), 3316; https://doi.org/10.3390/ijms20133316 - 05 Jul 2019
Abstract
Currently, there is increasing evidence linking diabetes mellitus (especially type 2 diabetes mellitus) with carcinogenesis through various biological processes, such as fat-induced chronic inflammation, hyperglycemia, hyperinsulinemia, and angiogenesis. Chemotherapeutic agents are used in the treatment of cancer, but in most cases, patients develop [...] Read more.
Currently, there is increasing evidence linking diabetes mellitus (especially type 2 diabetes mellitus) with carcinogenesis through various biological processes, such as fat-induced chronic inflammation, hyperglycemia, hyperinsulinemia, and angiogenesis. Chemotherapeutic agents are used in the treatment of cancer, but in most cases, patients develop resistance. Phenformin, an oral biguanide drug used to treat type 2 diabetes mellitus, was removed from the market due to a high risk of fatal lactic acidosis. However, it has been shown that phenformin is, with other biguanides, an authentic tumor disruptor, not only by the production of hypoglycemia due to caloric restriction through AMP-activated protein kinase with energy detection (AMPK) but also as a blocker of the mTOR regulatory complex. Moreover, the addition of phenformin eliminates resistance to antiangiogenic tyrosine kinase inhibitors (TKI), which prevent the uncontrolled metabolism of glucose in tumor cells. In this review, we evidence the great potential of phenformin as an anticancer agent. We thoroughly review its mechanism of action and clinical trial assays, specially focusing on current challenges and future perspectives of this promising drug. Full article
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Article
Title: The amuvatinib derivative, compound 6, inhibits mitochondria and kills tumor cells under glucose starvation
Authors: Barak Rotblat, etc.

Article
Title: Berberis vulgaris: a potential antidote against ifosfamide induced toxicities and synergist for its anticancer effect
Authors: Muhammad Usman Mirza, etc.

Review
Title: Anti-vascular agents in anticancer therapy
Authors: Ryszard Smolarczyk, etc.
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