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Tumor Resistance: Mechanisms and Therapy Advancements

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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: closed (31 August 2023) | Viewed by 8766

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Special Issue Editor

Dr. Ilya Ulasov

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Guest Editor

Institute for Regenerative Medicine, Sechenov First Moscow State Medical University, 119991 Moscow, Russia
Interests: cell death; gene therapy; autophagy; brain tumors; tumor resistance

Special Issue Information

Dear Colleagues,

The fast development of therapy resistance is a key roadblock to successful cancer treatment. While targeted therapies can improve overall survival in individuals, their effects are temporary. Some of the patients who react to these medicines at first develop resistance to them after a few months. Tumor cells without the driving mutation survive therapy and repopulate the tumor, according to multiple single-cell sequencing. Simultaneously, compensatory epigenetic and genetic modifications of most of the results in cell signaling reduce reliance on the targeted pathway, therefore promoting resistance. As a result, there is an urgent need for novel treatment approaches that might provide more effective cancer control. This special edition will focus on the new cell signaling mechanisms that regulate tumor resistance and escape from therapy, as well as novel anticancer therapy strategies.

Dr. Ilya Ulasov
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

therapy resistance
targeted therapies
tumor resistance

Published Papers (4 papers)

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Research

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21 pages, 4097 KiB

Open AccessArticle

Carotenoid-Enriched Nanoemulsions and γ-Rays Synergistically Induce Cell Death in a Novel Radioresistant Osteosarcoma Cell Line

by Maria Russo, Stefania Moccia, Carmela Spagnuolo, Idolo Tedesco and Gian Luigi Russo

Int. J. Mol. Sci. 2022, 23(24), 15959; https://doi.org/10.3390/ijms232415959 - 15 Dec 2022

Cited by 2 | Viewed by 1256

Abstract

We previously demonstrated that SAOS human osteosarcoma cells, incubated with carotenoid-enriched nanoemulsions (CEN), activated a nonprotective form of autophagy and delayed cell proliferation. The present work focuses on the biological effects of CEN on a derivative of SAOS cells named SAOS400, recently described for their radiation resistance and higher expression of therapy-induced senescence (TIS) markers. SAOS400 cells, incubated with CEN, activated a “cytostatic” form of autophagy confirmed by cell cycle arrest in the G2/M phase and increased expression of autophagic proteins. Treatment of SAOS400 cells with CEN also resulted in decreased expression of the senescence marker p16^INK4. However, when SAOS400 cells were γ-irradiated in combination with CEN, the threshold for cell death was reached (>60% after 96 h). We showed that this type of cell death corresponded to ‘cytotoxic’ or ‘lethal’ autophagy and that the combined treatment of CEN plus γ-rays was synergistic, with the combination index < 1. Since CEN contained β-carotene, the pure compound was used in SAOS400 cells at the same concentration present in CEN and up to 10 times higher. However, no radio-sensitizing effect of β-carotene was observed, suggesting that the biological effect of CEN was due to less abundant but more bioactive molecules, or to the synergistic activity of multiple components present in the extracts, confirming the functional pleiotropy of natural extracts enriched in bioactive molecules. Full article

(This article belongs to the Special Issue Tumor Resistance: Mechanisms and Therapy Advancements)

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Review

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17 pages, 1518 KiB

Open AccessReview

The Impact of Metformin on Tumor-Infiltrated Immune Cells: Preclinical and Clinical Studies

by Mohamed Abdelmoneim, Mona Alhussein Aboalela, Yoshinori Naoe, Shigeru Matsumura, Ibrahim Ragab Eissa, Itzel Bustos-Villalobos, Patricia Angela Sibal, Yuhei Takido, Yasuhiro Kodera and Hideki Kasuya

Int. J. Mol. Sci. 2023, 24(17), 13353; https://doi.org/10.3390/ijms241713353 - 28 Aug 2023

Cited by 3 | Viewed by 1679

Abstract

The tumor microenvironment (TME) plays a pivotal role in the fate of cancer cells, and tumor-infiltrating immune cells have emerged as key players in shaping this complex milieu. Cancer is one of the leading causes of death in the world. The most common standard treatments for cancer are surgery, radiation therapy, and chemotherapeutic drugs. In the last decade, immunotherapy has had a potential effect on the treatment of cancer patients with poor prognoses. One of the immune therapeutic targeted approaches that shows anticancer efficacy is a type 2 diabetes medication, metformin. Beyond its glycemic control properties, studies have revealed intriguing immunomodulatory properties of metformin. Meanwhile, several studies focus on the impact of metformin on tumor-infiltrating immune cells in various tumor models. In several tumor models, metformin can modulate tumor-infiltrated effector immune cells, CD8⁺, CD4⁺ T cells, and natural killer (NK) cells, as well as suppressor immune cells, T regulatory cells, tumor-associated macrophages (TAMs), and myeloid-derived suppressor cells (MDSCs). In this review, we discuss the role of metformin in modulating tumor-infiltrating immune cells in different preclinical models and clinical trials. Both preclinical and clinical studies suggest that metformin holds promise as adjunctive therapy in cancer treatment by modulating the immune response within the tumor microenvironment. Nonetheless, both the tumor type and the combined therapy have an impact on the specific targets of metformin in the TME. Further investigations are warranted to elucidate the precise mechanisms underlying the immunomodulatory effects of metformin and to optimize its clinical application in cancer patients. Full article

(This article belongs to the Special Issue Tumor Resistance: Mechanisms and Therapy Advancements)

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17 pages, 1471 KiB

Open AccessReview

VE-Cadherin in Cancer-Associated Angiogenesis: A Deceptive Strategy of Blood Vessel Formation

by Daniel Delgado-Bellido, F. J. Oliver, María Victoria Vargas Padilla, Laura Lobo-Selma, Antonio Chacón-Barrado, Juan Díaz-Martin and Enrique de Álava

Int. J. Mol. Sci. 2023, 24(11), 9343; https://doi.org/10.3390/ijms24119343 - 26 May 2023

Cited by 2 | Viewed by 1644

Abstract

Tumor growth depends on the vascular system, either through the expansion of blood vessels or novel adaptation by tumor cells. One of these novel pathways is vasculogenic mimicry (VM), which is defined as a tumor-provided vascular system apart from endothelial cell-lined vessels, and its origin is partly unknown. It involves highly aggressive tumor cells expressing endothelial cell markers that line the tumor irrigation. VM has been correlated with high tumor grade, cancer cell invasion, cancer cell metastasis, and reduced survival of cancer patients. In this review, we summarize the most relevant studies in the field of angiogenesis and cover the various aspects and functionality of aberrant angiogenesis by tumor cells. We also discuss the intracellular signaling mechanisms involved in the abnormal presence of VE-cadherin (CDH5) and its role in VM formation. Finally, we present the implications for the paradigm of tumor angiogenesis and how targeted therapy and individualized studies can be applied in scientific analysis and clinical settings. Full article

(This article belongs to the Special Issue Tumor Resistance: Mechanisms and Therapy Advancements)

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15 pages, 7559 KiB

Open AccessReview

Resistance to TOP-1 Inhibitors: Good Old Drugs Still Can Surprise Us

by Santosh Kumar and Michael Y. Sherman

Int. J. Mol. Sci. 2023, 24(8), 7233; https://doi.org/10.3390/ijms24087233 - 13 Apr 2023

Cited by 7 | Viewed by 3590

Abstract

Irinotecan (SN-38) is a potent and broad-spectrum anticancer drug that targets DNA topoisomerase I (Top1). It exerts its cytotoxic effects by binding to the Top1-DNA complex and preventing the re-ligation of the DNA strand, leading to the formation of lethal DNA breaks. Following the initial response to irinotecan, secondary resistance is acquired relatively rapidly, compromising its efficacy. There are several mechanisms contributing to the resistance, which affect the irinotecan metabolism or the target protein. In addition, we have demonstrated a major resistance mechanism associated with the elimination of hundreds of thousands of Top1 binding sites on DNA that can arise from the repair of prior Top1-dependent DNA cleavages. Here, we outline the major mechanisms of irinotecan resistance and highlight recent advancements in the field. We discuss the impact of resistance mechanisms on clinical outcomes and the potential strategies to overcome resistance to irinotecan. The elucidation of the underlying mechanisms of irinotecan resistance can provide valuable insights for the development of effective therapeutic strategies. Full article

(This article belongs to the Special Issue Tumor Resistance: Mechanisms and Therapy Advancements)

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