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Current Advances in the Discovery and Development of New Therapies against Cancer

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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 11011

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Special Issue Editor

Dr. Benjamin Pineda

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Guest Editor

National Institute of Neurology and Neurosurgery, Mexico City 14269, Mexico
Interests: tumor immunology; immunotherapy; tumor microenvironment

Special Issue Information

Dear Colleagues,

The treatment of cancer, including leukemias and solid tumors, is a challenging task, as there are only a few approved therapeutic options besides chemo-radiotherapy and surgery, that often fail at increasing the survival of patients. The ever changing nature of these disease, along with very few treatments available, has made it almost impossible to increase its outcome. For these reasons, researchers have been focused on the discovery, development, and possible mechanism of targeted therapies for cancer. Molecular targeted therapy, nanotherapy and immunotherapy are strategies that could be used alone or combined with the standard treatment, leading to a better outcome of the disease as well as an increase of survival.

The goal of this research topic is to provide a broad overview of the most recent advances in the discovery and development of therapies that could have the potential to target solid tumors and leukemias, as well as the repositioning of old drugs, initially used in other diseases, that could be used against these tumors.

The editors of this research topic welcome the submissions of high-quality original research articles, reviews and mini-reviews.

We are especially interested in receiving papers aimed at, but not limited to:

a) Development and discovery of new cancer drugs especially designed against solid tumors and leukemias.

b) Development and discovery of new cancer drugs especially designed against SNC tumors.

c) Development and discovery of new therapies that combine chemotherapeutic agents with molecular targeted therapy and agents that target genes and/or proteins involved in cellular metabolism.

d) Development and discovery of new therapies that combine chemotherapeutic agents with nanotherapy.

e) In vitro, in vivo and preclinical studies that show the use of new therapies (either alone or combined with the standard treatment) towards cancer.

f) In vitro, in vivo and preclinical studies that show drug repositioning towards cancer.

g) Reviews focused on the “state of art” of cancer drugs and new therapies against cancer.

Dr. Benjamin Pineda
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
solid tumor
leukemia
central nervous system
tumor
drug discovery
therapy
nanotherapy

Published Papers (6 papers)

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Research

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17 pages, 8071 KiB

Open AccessArticle

Selection and Identification of an ssDNA Aptamer for Fibroblast Activation Protein

by Xiaomin Zhang, Ge Yang, Yi Zhao, Xuyan Dai, Wenjing Liu, Feng Qu and Yuanyu Huang

Molecules 2023, 28(4), 1682; https://doi.org/10.3390/molecules28041682 - 09 Feb 2023

Cited by 2 | Viewed by 2286

Abstract

As a type II transmembrane serine protease, fibroblast activation protein (FAP) is specifically expressed on the surface of fibroblasts associated with a variety of epithelial-derived malignancies such as pancreatic cancer, breast cancer, and colon cancer. It participates in the processes of tumorigenesis, progression, and immunosuppression. FAP constitutes an important target for tumor treatment; however, the current studies on FAP are mainly related to structural characteristics, enzymatic properties, and biological functions, and aptamers of FAP have not been investigated. In this work, by using recombinant human FAP as the target, five candidate aptamers, which are AptFAP-A1, AptFAP-A2, AptFAP-A3, AptFAP-A4, and AptFAP-A5, were selected by capillary electrophoresis–systematic evolution of ligands by exponential enrichment (CE-SELEX), and their secondary structures were predicted to be mainly stem-loop. Moreover, the CE-laser-induced fluorescence (LIF) method was used to determine the equilibrium dissociation constant K_D values between the FAP protein and candidate aptamers, and the K_D value was in the low molar range. Finally, Cy5-labeled aptamers were co-incubated with human pancreatic cancer-associated fibroblasts highly expressing FAP protein, and confocal microscopy imaging showed that aptamer AptFAP-A4 had the highest affinities with the cells. The FAP aptamers screened in this study provide a promising direction for the development of rapid tumor diagnosis and targeted therapy. Full article

(This article belongs to the Special Issue Current Advances in the Discovery and Development of New Therapies against Cancer)

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16 pages, 1849 KiB

Open AccessArticle

Synthesis and Preclinical Evaluation of Small-Molecule Prostate-Specific Membrane Antigen-Targeted Abiraterone Conjugate

by Aleksei E. Machulkin, Ekaterina A. Nimenko, Nikolay U. Zyk, Anastasiia A. Uspenskaia, Galina B. Smirnova, Irina I. Khan, Vadim S. Pokrovsky, Alexander N. Vaneev, Roman V. Timoshenko, Vugara V. Mamed-Nabizade, Maria V. Zavertkina, Alexander Erofeev, Petr Gorelkin, Alexander G. Majouga, Nikolay V. Zyk, Elena S. Khazanova and Elena K. Beloglazkina

Molecules 2022, 27(24), 8795; https://doi.org/10.3390/molecules27248795 - 12 Dec 2022

Cited by 3 | Viewed by 1881

Abstract

Prostate cancer is the second most common type of cancer among men. The main method of its treatment is androgen deprivation therapy, which has a wide range of side effects. One of the solutions to this challenge is the targeted delivery of drugs to prostate cancer cells. In this study, we performed the synthesis of a novel small-molecule PSMA-targeted conjugate based on abiraterone. Cytotoxicity, the induction of intracellular reactive oxygen species, and P450-cytochrome species inhibition were investigated for this conjugate PSMA-abiraterone. The conjugate demonstrated a preferential effect on prostate tumor cells, remaining inactive at up to 100 µM in human fibroblast cells. In addition, it revealed preferential efficacy, specifically on PSMA-expressing lines with a 65% tumor growth inhibition level on 22Rv1 (PSMA+) xenografts after 14-fold oral administration of PSMA-Abi at a single dose of 500 mg/kg (7.0 g/kg total dose) was observed. This compound showed significantly reduced acute toxicity with comparable efficacy compared to AbiAc. Full article

(This article belongs to the Special Issue Current Advances in the Discovery and Development of New Therapies against Cancer)

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18 pages, 3182 KiB

Open AccessArticle

Anticancer Effect of Cathelicidin LL-37, Protegrin PG-1, Nerve Growth Factor NGF, and Temozolomide: Impact on the Mitochondrial Metabolism, Clonogenic Potential, and Migration of Human U251 Glioma Cells

by Alexandr N. Chernov, Tatiana A. Filatenkova, Ruslan I. Glushakov, Alexandra S. Buntovskaya, Diana A. Alaverdian, Anna N. Tsapieva, Alexandr V. Kim, Evgeniy V. Fedorov, Sofia S. Skliar, Marina V. Matsko, Elvira S. Galimova and Olga V. Shamova

Molecules 2022, 27(15), 4988; https://doi.org/10.3390/molecules27154988 - 05 Aug 2022

Cited by 5 | Viewed by 2079

Abstract

Glioblastoma (GBM) is one of the most aggressive and lethal malignancy of the central nervous system. Temozolomide is the standard of care for gliomas, frequently results in resistance to drug and tumor recurrence. Therefore, further research is required for the development of effective drugs in order to guarantee specific treatments to succeed. The aim of current study was to investigate the effects of nerve growth factor (NGF), human cathelicidin (LL-37), protegrin-1 (PG-1), and temozolomide on bioenergetic function of mitochondria, clonogenicity, and migration of human U251 glioma cells. Colony formation assay was used to test the ability of the glioma cells to form colonies in vitro. The U251 glioma cells migration was evaluated using wound-healing assay. To study the mitochondrial metabolism in glioma cells we measured oxygen consumption rates (OCR) and extracellular acidification rates (ECAR) using a Seahorse XF cell Mito stress test kit and Seahorse XF cell Glycolysis stress kit, respectively. We revealed that LL-37, NGF, and TMZ show strong anti-tumorigenic activity on GMB. LL-37 (4 μM), TMZ (155 μM), and NGF (7.55 × 10⁻³ μM) inhibited 43.9%–60.3%, 73.5%–81.3%, 66.2% the clonogenicity of glioma U251 cells for 1–2 days, respectively. LL-37 (4 μM), and NGF (7.55 × 10⁻³ μM) inhibited the migration of U251 glioma cells on the third and fourth days. TMZ also inhibited the migration of human glioma U251 cells over 1–3 days. In contrast, PG-1 (16 μM) stimulated the migration of U251 glioma cells on the second, fourth, and sixth days. Anti-mitogenic and anti-migration activities of NGF, LL-37, and TMZ maybe are relation to their capacity to reduce the basal OCR, ATP-synthetase, and maximal respiration of mitochondria in human glioma U251 cells. Glycolysis, glycolytic capacity and glycolytic spare in glioma U251 cells haven`t been changed under the effect of NGF, LL-37, PG-1, and TMZ in regard to control level. Thus, LL-37 and NGF inhibit migration and clonogenicity of U251 glioma cells, which may indicate that these compounds have anti-mitogenic and anti-migration effects on human glioma cells. The study of the mechanisms of these effects may contribute in the future to the use of NGF and LL-37 as therapeutic agents for gliomas. Full article

(This article belongs to the Special Issue Current Advances in the Discovery and Development of New Therapies against Cancer)

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Review

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18 pages, 1517 KiB

Open AccessReview

Predictive and Prognostic Biomarkers and Tumor Antigens for Targeted Therapy in Urothelial Carcinoma

by Aditya Eturi, Amman Bhasin, Kevin K. Zarrabi and William J. Tester

Molecules 2024, 29(8), 1896; https://doi.org/10.3390/molecules29081896 - 22 Apr 2024

Viewed by 420

Abstract

Urothelial carcinoma (UC) is the fourth most prevalent cancer amongst males worldwide. While patients with non-muscle-invasive disease have a favorable prognosis, 25% of UC patients present with locally advanced disease which is associated with a 10–15% 5-year survival rate and poor overall prognosis. Muscle-invasive bladder cancer (MIBC) is associated with about 50% 5 year survival when treated by radical cystectomy or trimodality therapy; stage IV disease is associated with 10–15% 5 year survival. Current therapeutic modalities for MIBC include neoadjuvant chemotherapy, surgery and/or chemoradiation, although patients with relapsed or refractory disease have a poor prognosis. However, the rapid success of immuno-oncology in various hematologic and solid malignancies offers new targets with tremendous therapeutic potential in UC. Historically, there were no predictive biomarkers to guide the clinical management and treatment of UC, and biomarker development was an unmet need. However, recent and ongoing clinical trials have identified several promising tumor biomarkers that have the potential to serve as predictive or prognostic tools in UC. This review provides a comprehensive summary of emerging biomarkers and molecular tumor targets including programmed death ligand 1 (PD-L1), epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), fibroblast growth factor receptor (FGFR), DNA damage response and repair (DDR) mutations, poly (ADP-ribose) polymerase (PARP) expression and circulating tumor DNA (ctDNA), as well as their clinical utility in UC. We also evaluate recent advancements in precision oncology in UC, while illustrating limiting factors and challenges related to the clinical application of these biomarkers in clinical practice. Full article

(This article belongs to the Special Issue Current Advances in the Discovery and Development of New Therapies against Cancer)

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22 pages, 2280 KiB

Open AccessReview

Abscopal Effect, Extracellular Vesicles and Their Immunotherapeutic Potential in Cancer Treatment

by Aleli Salazar, Víctor Chavarria, Itamar Flores, Samanta Ruiz, Verónica Pérez de la Cruz, Francisco Javier Sánchez-García and Benjamin Pineda

Molecules 2023, 28(9), 3816; https://doi.org/10.3390/molecules28093816 - 29 Apr 2023

Cited by 2 | Viewed by 1860

Abstract

The communication between tumor cells and the microenvironment plays a fundamental role in the development, growth and further immune escape of the tumor. This communication is partially regulated by extracellular vesicles which can direct the behavior of surrounding cells. In recent years, it has been proposed that this feature could be applied as a potential treatment against cancer, since several studies have shown that tumors treated with radiotherapy can elicit a strong enough immune response to eliminate distant metastasis; this phenomenon is called the abscopal effect. The mechanism behind this effect may include the release of extracellular vesicles loaded with damage-associated molecular patterns and tumor-derived antigens which activates an antigen-specific immune response. This review will focus on the recent discoveries in cancer cell communications via extracellular vesicles and their implication in tumor development, as well as their potential use as an immunotherapeutic treatment against cancer. Full article

(This article belongs to the Special Issue Current Advances in the Discovery and Development of New Therapies against Cancer)

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15 pages, 857 KiB

Open AccessReview

Role of STAT3 and NRF2 in Tumors: Potential Targets for Antitumor Therapy

by Yanjun Tian, Haiqing Liu, Mengwei Wang, Ruihao Wang, Guandong Yi, Meng Zhang and Ruijiao Chen

Molecules 2022, 27(24), 8768; https://doi.org/10.3390/molecules27248768 - 10 Dec 2022

Cited by 6 | Viewed by 1666

Abstract

Signal transducer and activator of transcription 3 (STAT3) and nuclear factor erythroid-derived 2-like 2 (NRF2, also known as NFE2L2), are two of the most complicated transcription regulators, which participate in a variety of physiological processes. Numerous studies have shown that they are overactivated in multiple types of tumors. Interestingly, STAT3 and NRF2 can also interact with each other to regulate tumor progression. Hence, these two important transcription factors are considered key targets for developing a new class of antitumor drugs. This review summarizes the pivotal roles of the two transcription regulators and their interactions in the tumor microenvironment to identify potential antitumor drug targets and, ultimately, improve patients’ health and survival. Full article

(This article belongs to the Special Issue Current Advances in the Discovery and Development of New Therapies against Cancer)

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