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Cancers
Special Issues
Overcoming Drug Resistance to Systemic Therapy in Breast Cancer
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Overcoming Drug Resistance to Systemic Therapy in Breast Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (15 October 2024) | Viewed by 3131

Special Issue Editors

Dr. Nethaji Muniraj

E-Mail Website
Guest Editor
Children’s National Hospital, Center for Cancer and Immunology Research, Washington, DC, USA
Interests: biochemistry; molecular biology; molecular immunology; cancer; tumor microenvironment; obesity; cancer immunology; cell therapy (CAR-NK and CAR_T cell therapy)
Special Issues, Collections and Topics in MDPI journals
Dr. Dimiter B. Avtanski

E-Mail Website
Guest Editor
Friedman Diabetes Institute, Lenox Hill Hospital, Northwell Health, New York, NY 10022, USA
Interests: breast cancer; EMT; obesity; cytokines; inflammation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Breast cancer is the second most common malignancy in women worldwide. The cause of cancer is multifactorial. The early diagnosis and appropriate treatment of cancer can improve the chances of survival. Other methods of early detection include self-examination, clinical breast examination, and imaging tests such as ultrasound and MRI. Breast cancer is a heterogeneous disease that is considered complex, as there is great diversity within tumors. Despite extensive research, the exact etiology of the disease has not yet been elucidated, as the identified genetic and epigenetic interactions cannot explain the cause of breast cancer in most cases. The existing treatment offers a minimal solution to drug resistance. Thus, there must be an unexplored pathway that contributes to the development of breast cancer. Hence, there is a necessity for novel research to discover a more effective therapeutic approach.

This Special Issue will explore the current state of research in the field of drug resistance, including the mechanisms of drug resistance, the development of new drugs and immunotherapies, and the potential for combination therapies. It will also discuss the challenges associated with drug resistance and the strategies that can be used to address them. Finally, the Special Issue will consider the implications of drug resistance for public health and the need for new approaches to combat this growing problem.

Dr. Nethaji Muniraj
Dr. Dimiter B. Avtanski
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 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 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. Cancers 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 2900 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

  • breast cancer
  • triple negative breast cancer
  • breast cancer stem cells
  • tumor microenvironment
  • drug resistance
  • immunotherapy
  • hormone therapy
  • targeted therapy
  • diagnosis and prevention
  • bioactive compounds

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Published Papers (2 papers)

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Research

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26 pages, 3517 KiB  
Article
HDAC6 as a Prognostic Factor and Druggable Target in HER2-Positive Breast Cancer
by Michela Cortesi, Sara Bravaccini, Sara Ravaioli, Elisabetta Petracci, Davide Angeli, Maria Maddalena Tumedei, William Balzi, Francesca Pirini, Michele Zanoni, Paola Possanzini, Andrea Rocca, Michela Palleschi, Paola Ulivi, Giovanni Martinelli and Roberta Maltoni
Cancers 2024, 16(22), 3752; https://doi.org/10.3390/cancers16223752 - 6 Nov 2024
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Abstract
Background: Adjuvant trastuzumab is the standard of care for HER2+ breast cancer (BC) patients. However, >50% of patients become resistant. This study aimed at the identification of the molecular factors associated with disease relapse and their further investigation as therapeutically exploitable targets. Methods: [...] Read more.
Background: Adjuvant trastuzumab is the standard of care for HER2+ breast cancer (BC) patients. However, >50% of patients become resistant. This study aimed at the identification of the molecular factors associated with disease relapse and their further investigation as therapeutically exploitable targets. Methods: Analyses were conducted on formalin-fixed paraffin-embedded tissues of the primary tumors of relapsed (cases) and not relapsed (controls) HER2+ BC patients treated with adjuvant trastuzumab. The nCounter Human Breast Cancer Panel 360 was used. Logistic regression and partitioning around medoids were employed to identify the genes associated with disease recurrence. Cytotoxicity experiments using trastuzumab-resistant cell lines and a network pharmacology approach were carried out to investigate drug efficacy. Results: A total of 52 patients (26 relapsed and 26 not relapsed) were analyzed. We found that a higher expression of HDAC6 was significantly associated with an increased risk of recurrence, with an adjusted OR of 3.20 (95% CI 1.38–9.91, p = 0.016). Then, we investigated the cytotoxic activity of the selective HDAC6 inhibitor Nexturastat A (NextA) on HER2+ cell lines, which were both sensitive and trastuzumab-resistant. A sub-cytotoxic concentration of NextA, combined with trastuzumab, showed a synergistic effect on BC cell lines. Finally, using a network pharmacology approach, we identified HSP90AA1 as the putative molecular candidate responsible for the synergism observed in vitro. Conclusions: Our findings encourage the exploration of the role of HDAC6 as a prognostic factor and the combinatorial use of HDAC6 selective inhibitors combined with trastuzumab in HER2+ BC, in particular for those patients experiencing drug resistance. Full article
(This article belongs to the Special Issue Overcoming Drug Resistance to Systemic Therapy in Breast Cancer)
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Review

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21 pages, 1657 KiB  
Review
Unleashing the Power of Yes-Associated Protein in Ferroptosis and Drug Resistance in Breast Cancer, with a Special Focus on Therapeutic Strategies
by RamaRao Malla, Durga Bhavani Kundrapu, Priyamvada Bhamidipati, Ganji Purnachandra Nagaraju and Nethaji Muniraj
Cancers 2023, 15(24), 5728; https://doi.org/10.3390/cancers15245728 - 6 Dec 2023
Viewed by 1673
Abstract
The YAP protein is a critical oncogenic mediator within the Hippo signaling pathway and has been implicated in various cancer types. In breast cancer, it frequently becomes activated, thereby contributing to developing drug-resistance mechanisms. Recent studies have underscored the intricate interplay between YAP [...] Read more.
The YAP protein is a critical oncogenic mediator within the Hippo signaling pathway and has been implicated in various cancer types. In breast cancer, it frequently becomes activated, thereby contributing to developing drug-resistance mechanisms. Recent studies have underscored the intricate interplay between YAP and ferroptosis within the breast tumor microenvironment. YAP exerts a negative regulatory effect on ferroptosis, promoting cancer cell survival and drug resistance. This review offers a concise summary of the current understanding surrounding the interplay between the YAP pathway, ferroptosis, and drug-resistance mechanisms in both bulk tumor cells and cancer stem cells. We also explore the potential of natural compounds alone or in combination with anticancer therapies for targeting the YAP pathway in treating drug-resistant breast cancer. This approach holds the promise of enhancing the effectiveness of current treatments and paving the way for developing novel therapeutics. Full article
(This article belongs to the Special Issue Overcoming Drug Resistance to Systemic Therapy in Breast Cancer)
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