Submit to Molecules Review for Molecules Propose a Special Issue

Journal Browser

► Journal Browser

Cancer Metabolism as a Target for New Oncological Drugs

Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (29 February 2024) | Viewed by 13310

Share This Special Issue

Special Issue Editor

Dr. Katarzyna Wiktorska

E-Mail Website
Guest Editor

Department of Biomedical Research, National Medicines Institute, Chełmska 30/34, 00-725 Warsaw, Poland
Interests: anticancer agent; cell metabolism; sulforaphane; nutrients; drug development and discovery; nanotechnology; cell death; cancer cell biology; drug–drug Interactions; breast cancer; chemoprevention

Special Issue Information

Dear Colleagues,

Cancer is a disease that still challenges physicians and scientists. Malignant transformation and tumor development require cell metabolism reprogramming, which distinguishes cancer cells from normal cells. The xenobiotic metabolism alteration of cancer cells also leads to the development of multi-drug resistance, which constitutes a major difficulty in the effective treatment of cancer. Advances in new technologies and our knowledge in this field can more accurately challenge molecular differences between normal and cancer/metastatic cells metabolism. This fascinating phenomenon raises perspectives for future tailored cancer therapies that exploit rationally designed new therapeutics, patient stratification, or dietary interventions.

Therefore, this Special Issue aims to gather the latest scientific advances in the field of cancer metabolism regarding its perspectives as a target for new oncological procedures.

This area covers but is not limited to the search for molecules within metabolites or metabolic pathways that might be targeted by drugs or alter their action, and for compounds that target defined metabolic pathways. All types of research are encouraged: from in silico studies, through all varieties of in vitro and in vivo research to epidemiological, prospective, and retrospective clinical studies.

Dr. Katarzyna Wiktorska
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. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). 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 metabolism
drug screening
xenobiotics metabolism
drug targets
metabolomics
metabolic pathways
multi-drug resistance
oncology

Published Papers (5 papers)

Download All Papers

Research

Jump to: Review

13 pages, 1550 KiB

Open AccessArticle

An Organofluorine Isoselenocyanate Analogue of Sulforaphane Affects Antimetabolite 5-Fluorouracil’s Anticancer Activity: A Perspective for New Combinatory Therapy in Triple-Negative Breast Cancer

by Małgorzata Milczarek, Tomasz Cierpiał, Piotr Kiełbasiński, Milena Małecka-Giełdowska, Marta Świtalska, Joanna Wietrzyk, Maciej Mazur and Katarzyna Wiktorska

Molecules 2023, 28(15), 5808; https://doi.org/10.3390/molecules28155808 - 1 Aug 2023

Cited by 1 | Viewed by 998

Abstract

Antimetabolites, especially 5-fluorouracil, are commonly used clinically to treat breast, colon, and other cancers. However, their side effects and inefficiency in monotherapy have prompted further searches for new combinations. Thus, the anticancer effect of 5-fluorouracil (5-FU) and the sulforaphane analogue, 4-isoselenocyanato-1-butyl 4′-fluorobenzyl sulfoxide (ISC), were tested in in vitro and in vivo models of triple-negative breast cancer (TNBC) as a new option for this treatment-resistant and aggressive type of breast cancer. A synergic interaction between 5-FU and ISC was observed in the TNBC in vitro model MDA-MB-231 cell line, which led to enhanced antiproliferative effects. The results of in vitro studies were confirmed by in vivo tests, which demonstrated stronger tumor growth inhibition and additive interactions between 5-FU and ISC in the murine TNBC model. Moreover, the results of the body mass and blood analysis showed the safety of the tested combination. The mechanistic study revealed that the combined treatment triggered apoptosis and necrosis, as well as inhibited cell migration. Full article

(This article belongs to the Special Issue Cancer Metabolism as a Target for New Oncological Drugs)

► Show Figures

Graphical abstract

16 pages, 3939 KiB

Open AccessArticle

Design of Novel Coumarin Derivatives as NUDT5 Antagonists That Act by Restricting ATP Synthesis in Breast Cancer Cells

by Vidya Niranjan, Sanjana Jayaprasad, Akshay Uttarkar, Raviraj Kusanur and Jitendra Kumar

Molecules 2023, 28(1), 89; https://doi.org/10.3390/molecules28010089 - 22 Dec 2022

Cited by 8 | Viewed by 1985

Abstract

Breast cancer, a heterogeneous disease, is among the most frequently diagnosed diseases and is the second leading cause of death due to cancer among women after lung cancer. Phytoactives (plant-based derivatives) and their derivatives are safer than synthetic compounds in combating chemoresistance. In the current work, a template-based design of the coumarin derivative was designed to target the ADP-sugar pyrophosphatase protein. The novel coumarin derivative (2R)-2-((S)-sec-butyl)-5-oxo-4-(2-oxochroman-4-yl)-2,5-dihydro-1H-pyrrol-3-olate was designed. Molecular docking studies provided a docking score of −6.574 kcal/mol and an MM-GBSA value of −29.15 kcal/mol. Molecular dynamics simulation studies were carried out for 500 ns, providing better insights into the interaction. An RMSD change of 2.4 Å proved that there was a stable interaction and that there was no conformational change induced to the receptor. Metadynamics studies were performed to calculate the unbinding energy of the principal compound with NUDT5, which was found to be −75.171 kcal/mol. In vitro validation via a cytotoxicity assay (MTT assay) of the principal compound was carried out with quercetin as a positive control in the MCF7 cell line and with an IC₅₀ value of 55.57 (+/−) 0.7 μg/mL. This work promoted the research of novel natural derivatives to discover their anticancer activity. Full article

(This article belongs to the Special Issue Cancer Metabolism as a Target for New Oncological Drugs)

► Show Figures

Figure 1

Review

Jump to: Research

28 pages, 3437 KiB

Open AccessReview

Metabolic Rewiring in Cancer: Small Molecule Inhibitors in Colorectal Cancer Therapy

by Domiziana Masci, Michela Puxeddu, Romano Silvestri and Giuseppe La Regina

Molecules 2024, 29(9), 2110; https://doi.org/10.3390/molecules29092110 - 2 May 2024

Viewed by 458

Abstract

Alterations in cellular metabolism, such as dysregulation in glycolysis, lipid metabolism, and glutaminolysis in response to hypoxic and low-nutrient conditions within the tumor microenvironment, are well-recognized hallmarks of cancer. Therefore, understanding the interplay between aerobic glycolysis, lipid metabolism, and glutaminolysis is crucial for developing effective metabolism-based therapies for cancer, particularly in the context of colorectal cancer (CRC). In this regard, the present review explores the complex field of metabolic reprogramming in tumorigenesis and progression, providing insights into the current landscape of small molecule inhibitors targeting tumorigenic metabolic pathways and their implications for CRC treatment. Full article

(This article belongs to the Special Issue Cancer Metabolism as a Target for New Oncological Drugs)

► Show Figures

Figure 1

18 pages, 667 KiB

Open AccessReview

Review to Understand the Crosstalk between Immunotherapy and Tumor Metabolism

by Pratibha Pandey, Fahad Khan, Tarun Kumar Upadhyay and Ramish Maqsood

Molecules 2023, 28(2), 862; https://doi.org/10.3390/molecules28020862 - 15 Jan 2023

Cited by 4 | Viewed by 2296

Abstract

Immune checkpoint inhibitors have ushered in a new era of cancer treatment by increasing the likelihood of long-term survival for patients with metastatic disease and by introducing fresh therapeutic indications in cases where the disease is still in its early stages. Immune checkpoint inhibitors that target the proteins cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) or programmed death-1/programmed death ligand-1 have significantly improved overall survival in patients with certain cancers and are expected to help patients achieve complete long-lasting remissions and cures. Some patients who receive immune checkpoint inhibitors, however, either experience therapeutic failure or eventually develop immunotherapy resistance. Such individuals are common, which necessitates a deeper understanding of how cancer progresses, particularly with regard to nutritional regulation in the tumor microenvironment (TME), which comprises metabolic cross-talk between metabolites and tumor cells as well as intracellular metabolism in immune and cancer cells. Combination of immunotherapy with targeted metabolic regulation might be a focus of future cancer research despite a lack of existing clinical evidence. Here, we reviewed the significance of the tumor microenvironment and discussed the most significant immunological checkpoints that have recently been identified. In addition, metabolic regulation of tumor immunity and immunological checkpoints in the TME, including glycolysis, amino acid metabolism, lipid metabolism, and other metabolic pathways were also incorporated to discuss the possible metabolism-based treatment methods being researched in preclinical and clinical settings. This review will contribute to the identification of a relationship or crosstalk between tumor metabolism and immunotherapy, which will shed significant light on cancer treatment and cancer research. Full article

(This article belongs to the Special Issue Cancer Metabolism as a Target for New Oncological Drugs)

► Show Figures

Figure 1

18 pages, 2057 KiB

Open AccessReview

Potential of Kalanchoe pinnata as a Cancer Treatment Adjuvant and an Epigenetic Regulator

by Marta Elena Hernández-Caballero, José Alfredo Sierra-Ramírez, Ricardo Villalobos-Valencia and Emmanuel Seseña-Méndez

Molecules 2022, 27(19), 6425; https://doi.org/10.3390/molecules27196425 - 29 Sep 2022

Cited by 8 | Viewed by 6460

Abstract

Cancer is a global public health problem that is related to different environmental and lifestyle factors. Although the combination of screening, prevention, and treatment of cancer has resulted in increased patient survival, conventional treatments sometimes have therapeutic limitations such as resistance to drugs or severe side effects. Oriental culture includes herbal medicine as a complementary therapy in combination with chemotherapy or radiotherapy. This study aimed to identify the bioactive ingredients in Kalanchoe pinnata, a succulent herb with ethnomedical applications for several diseases, including cancer, and reveal its anticancer mechanisms through a molecular approach. The herb contains gallic acid, caffeic acid, coumaric acid, quercetin, quercitrin, isorhamnetin, kaempferol, bersaldegenin, bryophyllin a, bryophyllin c, bryophynol, bryophyllol and bryophollone, stigmasterol, campesterol, and other elements. Its phytochemicals participate in the regulation of proliferation, apoptosis, cell migration, angiogenesis, metastasis, oxidative stress, and autophagy. They have the potential to act as epigenetic drugs by reverting the acquired epigenetic changes associated with tumor resistance to therapy—such as the promoter methylation of suppressor genes, inhibition of DNMT1 and DNMT3b activity, and HDAC regulation—through methylation, thereby regulating the expression of genes involved in the PI3K/Akt/mTOR, Nrf2/Keap1, MEK/ERK, and Wnt/β-catenin pathways. All of the data support the use of K. pinnata as an adjuvant in cancer treatment. Full article

(This article belongs to the Special Issue Cancer Metabolism as a Target for New Oncological Drugs)

► Show Figures