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Advances in Pharmacotherapeutic Strategies to Prevent Tumor Development, Progression and Treatment Resistance

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A special issue of Current Issues in Molecular Biology (ISSN 1467-3045). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: 31 May 2024 | Viewed by 1821

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Special Issue Editor

Dr. Peter C. Hart

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Guest Editor

College of Pharmacy, Roosevelt University, 1400 N Roosevelt Blvd, Schaumburg, IL 60173, USA
Interests: tumor microenvironment; cell–cell signaling; cell metabolism; hypoxia; oxidative stress; drug repurposing; ovarian cancer; breast cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Recent advances in our understanding of the molecular mechanisms underlying cancer progression have promoted the de novo development of novel small molecules and facilitated drug repositioning to complement contemporary therapeutic approaches to enhance patient survival. Pharmacotherapeutics that target nonredundant pathways in tumor cells required for proliferation, survival and unchecked self-renewal capacity have provided additional strategies to improve standard of care in treating many forms of cancer. Moreover, appreciating the importance of targeting the stromal compartment (e.g., immune cells, fibroblasts, adipocytes) has further exposed therapeutic liabilities in the tumor microenvironment that may present additional options to prevent tumor cell growth and suppress cancer cell resistance to therapeutics. Further identification and elaboration of necessary intracellular pathways and cell–cell signaling mechanisms may inform new pharmacotherapeutic approaches to prevent tumor development, progression, and treatment resistance to build on currently available clinical strategies.

This issue of Current Issues in Molecular Biology is open to both original research articles and review articles focused on the advances in our understanding of actionable mechanisms for pharmacologic exploitation to prevent cancer development and progression. Identifying and elaborating on these mechanisms may provide a path forward in improving patient care and outcomes.

Dr. Peter C. Hart
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. Current Issues in Molecular Biology is an international peer-reviewed open access monthly 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 2200 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
therapeutic resistance
drug tolerance
mechanisms of tumor development
mechanisms of tumor progression

Published Papers (4 papers)

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Research

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15 pages, 923 KiB

Open AccessArticle

Low Cell Bioenergetic Metabolism Characterizes Chronic Lymphocytic Leukemia Patients with Unfavorable Genetic Factors and with a Better Response to BTK Inhibition

by Simone Mirabilii, Monica Piedimonte, Esmeralda Conte, Daniele Mirabilii, Francesca Maria Rossi, Riccardo Bomben, Antonella Zucchetto, Valter Gattei, Agostino Tafuri and Maria Rosaria Ricciardi

Curr. Issues Mol. Biol. 2024, 46(6), 5085-5099; https://doi.org/10.3390/cimb46060305 - 22 May 2024

Viewed by 330

Abstract

Chronic Lymphocytic Leukemia (CLL) is an indolent malignancy characterized by the accumulation of quiescent mature B cells. However, these cells are transcriptionally and translationally active, implicating an active metabolism. The recent literature suggests that CLL cells have an oxidative-type phenotype. Given the role of cell metabolism, which is able to influence the outcome of treatments, in other neoplasms, we aimed to assess its prognostic role in CLL patients by determining the ex vivo bioenergetic metabolic profile of CLL cells, evaluating the correlation with the patient clinical/biological characteristics and the in vivo response to BTK inhibitor treatment. Clustering analysis of primary samples identified two groups, characterized by low (CLL low) or high (CLL high) bioenergetic metabolic rates. Compared to the CLL high, CLL with lower bioenergetic metabolic rates belonged to patients characterized by a statistically significant higher white blood cell count and by unfavorable molecular genetics. More importantly, patients in the CLL low cluster displayed a better and more durable response to the BTK inhibitor ibrutinib, thus defining a bioenergetic metabolic subgroup that can benefit the most from this therapy. Full article

(This article belongs to the Special Issue Advances in Pharmacotherapeutic Strategies to Prevent Tumor Development, Progression and Treatment Resistance)

17 pages, 5527 KiB

Open AccessArticle

The Biological Impact of Some Phosphonic and Phosphinic Acid Derivatives on Human Osteosarcoma

by Zakzak Khaled, Gheorghe Ilia, Claudia Watz, Ioana Macașoi, George Drăghici, Vasile Simulescu, Petru Eugen Merghes, Narcis Ion Varan, Cristina Adriana Dehelean, Lavinia Vlaia and Laurențiu Sima

Curr. Issues Mol. Biol. 2024, 46(5), 4815-4831; https://doi.org/10.3390/cimb46050290 - 15 May 2024

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Abstract

Osteosarcoma malignancy currently represents a major health problem; therefore, the need for new therapy approaches is of great interest. In this regard, the current study aims to evaluate the anti-neoplastic potential of a newly developed phosphinic acid derivative (2-carboxyethylphenylphosphinic acid) and, subsequently, to outline its pharmaco-toxicological profile by employing two different in vitro human cell cultures (keratinocytes—HaCaT—and osteosarcoma SAOS-2 cells), employing different techniques (MTT assay, cell morphology assessment, LDH assay, Hoechst staining and RT-PCR). Additionally, the results obtained are compared with three commercially available phosphorus-containing compounds (P1, P2, P3). The results recorded for the newly developed compound (P4) revealed good biocompatibility (cell viability of 77%) when concentrations up to 5 mM were used on HaCaT cells for 24 h. Also, the HaCaT cultures showed no significant morphological alterations or gene modulation, thus achieving a biosafety profile even superior to some of the commercial products tested herein. Moreover, in terms of anti-osteosarcoma activity, 2-carboxyethylphenylphosphinic acid expressed promising activity on SAOS-2 monolayers, the cells showing viability of only 55%, as well as apoptosis features and important gene expression modulation, especially Bid downregulation. Therefore, the newly developed compound should be considered a promising candidate for further in vitro and in vivo research related to osteosarcoma therapy. Full article

(This article belongs to the Special Issue Advances in Pharmacotherapeutic Strategies to Prevent Tumor Development, Progression and Treatment Resistance)

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14 pages, 6895 KiB

Open AccessCommunication

Stemness and Cell Cycle Regulators and Their Modulation by Retinoic Acid in Ewing Sarcoma

by Maria Eduarda Battistella, Natália Hogetop Freire, Bruno Toson, Matheus Dalmolin, Marcelo A. C. Fernandes, Isadora D. Tassinari, Mariane Jaeger, André T. Brunetto, Algemir L. Brunetto, Lauro Gregianin, Caroline Brunetto de Farias and Rafael Roesler

Curr. Issues Mol. Biol. 2024, 46(5), 3990-4003; https://doi.org/10.3390/cimb46050246 - 26 Apr 2024

Viewed by 486

Abstract

Retinoic acid (RA) regulates stemness and differentiation in human embryonic stem cells (ESCs). Ewing sarcoma (ES) is a pediatric tumor that may arise from the abnormal development of ESCs. Here we show that RA impairs the viability of SK-ES-1 ES cells and affects the cell cycle. Cells treated with RA showed increased levels of p21 and its encoding gene, CDKN1A. RA reduced mRNA and protein levels of SRY-box transcription factor 2 (SOX2) as well as mRNA levels of beta III Tubulin (TUBB3), whereas the levels of CD99 increased. Exposure to RA reduced the capability of SK-ES-1 to form tumorspheres with high expression of SOX2 and Nestin. Gene expression of CD99 and CDKN1A was reduced in ES tumors compared to non-tumoral tissue, whereas transcript levels of SOX2 were significantly higher in tumors. For NES and TUBB3, differences between tumors and control tissue did not reach statistical significance. Low expression of CD99 and NES, and high expression of SOX2, were significantly associated with a poorer patient prognosis indicated by shorter overall survival (OS). Our results indicate that RA may display rather complex modulatory effects on multiple target genes associated with the maintenance of stem cell’s features versus their differentiation, cell cycle regulation, and patient prognosis in ES. Full article

(This article belongs to the Special Issue Advances in Pharmacotherapeutic Strategies to Prevent Tumor Development, Progression and Treatment Resistance)

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Review

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18 pages, 3159 KiB

Open AccessReview

Changing the Landscape of Solid Tumor Therapy from Apoptosis-Promoting to Apoptosis-Inhibiting Strategies

by Razmik Mirzayans

Curr. Issues Mol. Biol. 2024, 46(6), 5379-5396; https://doi.org/10.3390/cimb46060322 - 28 May 2024

Viewed by 98

Abstract

The many limitations of implementing anticancer strategies under the term “precision oncology” have been extensively discussed. While some authors propose promising future directions, others are less optimistic and use phrases such as illusion, hype, and false hypotheses. The reality is revealed by practicing clinicians and cancer patients in various online publications, one of which has stated that “in the quest for the next cancer cure, few researchers bother to look back at the graveyard of failed medicines to figure out what went wrong”. The message is clear: Novel therapeutic strategies with catchy names (e.g., synthetic “lethality”) have not fulfilled their promises despite decades of extensive research and clinical trials. The main purpose of this review is to discuss key challenges in solid tumor therapy that surprisingly continue to be overlooked by the Nomenclature Committee on Cell Death (NCCD) and numerous other authors. These challenges include: The impact of chemotherapy-induced genome chaos (e.g., multinucleation) on resistance and relapse, oncogenic function of caspase 3, cancer cell anastasis (recovery from late stages of apoptosis), and pitfalls of ubiquitously used preclinical chemosensitivity assays (e.g., cell “viability” and tumor growth delay studies in live animals) that score such pro-survival responses as “lethal” events. The studies outlined herein underscore the need for new directions in the management of solid tumors. Full article

(This article belongs to the Special Issue Advances in Pharmacotherapeutic Strategies to Prevent Tumor Development, Progression and Treatment Resistance)

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