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Biomolecules
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Molecular Targets for Breast Cancer Therapy
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Molecular Targets for Breast Cancer Therapy

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: closed (29 February 2024) | Viewed by 8962

Special Issue Editor

Dr. Hamidreza Montazeri Aliabadi

E-Mail Website
Guest Editor
Department of Biomedical and Pharmaceutical Sciences, Chapman University School of Pharmacy, Harry and Diane Rinker Health Science Campus, Irvine, CA 92618, USA
Interests: pharmaceutics; targeted delivery; RNA interference; cancer biology; signaling pathways
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

After the cytotoxic chemotherapy era that was stained with horrific toxicities and multi-drug resistance, “molecularly targeted drugs” brought new hope to the battle against cancer. However, despite the occasional introduction of new drugs, resistance seems to be inevitable. A sub-population of the tumor cells often fails to respond favorably to the initial treatment (likely due to tumor cell heterogeneity causing intrinsic resistance). This “Darwinian clone selection” is documented in different types of cancer in response to a variety of molecularly targeted drugs. On the other hand, initially responsive cells become resistant shortly after repeated doses (acquired resistance), which, in addition to point mutations, could be due to the plasticity of cancer cells that have access to a variety of signaling pathways that can compensate for the targeted protein. Therefore, the identification of new targets is crucial for overcoming these obstacles. This Special Issue focuses on breast cancer and sheds the spotlight on the most recent efforts in the identification of novel molecular targets or the newly discovered crosstalk among the established signaling pathways. Our goal is to create a platform to present information about the molecular mechanism(s) involved in the proliferation, survival, and/or resistance in breast cancer cells that can lead to new treatment strategies.

Dr. Hamidreza Montazeri Aliabadi
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. Biomolecules 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 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

  • breast cancer
  • molecular targets
  • signaling pathways
  • proliferation
  • survival
  • resistance
  • crosstalk

Related Special Issue

Published Papers (5 papers)

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Research

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20 pages, 4666 KiB  
Article
Designing Nanomedicines for Breast Cancer Therapy
by Saba Abbasi Dezfouli, Amarnath P. Rajendran, Jillian Claerhout and Hasan Uludag
Biomolecules 2023, 13(10), 1559; https://doi.org/10.3390/biom13101559 - 22 Oct 2023
Viewed by 1277
Abstract
In 2020, breast cancer became the most diagnosed cancer worldwide. Conventional chemotherapies have major side effects due to their non-specific activities. Alternatively, short interfering RNA(siRNA)-carrying nanoparticles (NPs) have a high potential to overcome this non-specificity. Lipid-substituted polyethyleneimine (PEI) polymers (lipopolymers) have been reported [...] Read more.
In 2020, breast cancer became the most diagnosed cancer worldwide. Conventional chemotherapies have major side effects due to their non-specific activities. Alternatively, short interfering RNA(siRNA)-carrying nanoparticles (NPs) have a high potential to overcome this non-specificity. Lipid-substituted polyethyleneimine (PEI) polymers (lipopolymers) have been reported as efficient non-viral carriers of siRNA. This study aims to engineer novel siRNA/lipopolymer nanocomplexes by incorporating anionic additives to obtain gene silencing through siRNA activity with minimal nonspecific toxicity. We first optimized our polyplexes in GFP+ MDA-MB-231 cells to effectively silence the GFP gene. Inclusion of phosphate buffer with pH 8.0 as complex preparation media and N-Lauroylsarcosine Sodium Salt as additive, achieved ~80% silencing with the least amount of undesired cytotoxicity, which was persistent for at least 6 days. The survivin gene was then selected as a target in MDA-MB-231 cells since there is no strong drug (i.e., small organic molecule) for inhibition of its oncogenic activity. The qRT-PCR, flow cytometry analysis and MTT assay revealed >80% silencing, ~95% cell uptake and >70% cell killing by the same formulation. We conclude that our lipopolymer can be further investigated as a lead non-viral carrier for breast cancer gene therapy. Full article
(This article belongs to the Special Issue Molecular Targets for Breast Cancer Therapy)
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18 pages, 1719 KiB  
Article
The Expression of Trace Amine-Associated Receptors (TAARs) in Breast Cancer Is Coincident with the Expression of Neuroactive Ligand–Receptor Systems and Depends on Tumor Intrinsic Subtype
by Anastasia N. Vaganova, Daria D. Maslennikova, Valeria V. Konstantinova, Evgeny V. Kanov and Raul R. Gainetdinov
Biomolecules 2023, 13(9), 1361; https://doi.org/10.3390/biom13091361 - 07 Sep 2023
Cited by 1 | Viewed by 1220
Abstract
Currently, the contribution of trace amine-associated receptors (TAARs) to breast cancer (BC) is recognized, but their associations with various pathological characteristics are not yet understood. There is accumulated transcriptomic data for BC tumors, which are represented in publicly accessible databases. We estimated TAARs’ [...] Read more.
Currently, the contribution of trace amine-associated receptors (TAARs) to breast cancer (BC) is recognized, but their associations with various pathological characteristics are not yet understood. There is accumulated transcriptomic data for BC tumors, which are represented in publicly accessible databases. We estimated TAARs’ (including TAAR1, TAAR2, TAAR5, TAAR6, TAAR8, and TAAR9) associations with BC stage, grade, and molecular subtypes in these data and identified that the expression of all TAARs was associated with more unfavorable cancer subtypes, including basal-like and HER2-positive tumors. Also, the significant upregulation of all TAARs was demonstrated in circulating tumor cells compared to the metastatic lesions. Considering that co-expressed genes are more likely to be involved in the same biologic processes, we analyzed genes that are co-expressed with TAARs in BC. These gene sets were enriched with the genes of the olfactory transduction pathway and neuroactive ligand–receptor interaction participants. TAARs are co-expressed with G-protein-coupled receptors of monoamine neurotransmitters including dopamine, norepinephrine, and serotonin as well as with other neuroactive ligand-specific receptors. Since TAAR1 is able to modulate the activity of monoamine receptors that are involved in the regulation of BC growth, TAAR1 and potentially other TAARs may be regarded as prospective therapeutic targets for breast cancer. Full article
(This article belongs to the Special Issue Molecular Targets for Breast Cancer Therapy)
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19 pages, 6248 KiB  
Article
Adenosine/β-Cyclodextrin-Based Metal–Organic Frameworks as a Potential Material for Cancer Therapy
by Rajaram Rajamohan, Sekar Ashokkumar, Mani Murali Krishnan, Kuppusamy Murugavel, Moorthiraman Murugan and Yong Rok Lee
Biomolecules 2023, 13(7), 1154; https://doi.org/10.3390/biom13071154 - 20 Jul 2023
Cited by 3 | Viewed by 1521
Abstract
Recently, researchers have employed metal–organic frameworks (MOFs) for loading pharmaceutically important substances. MOFs are a novel class of porous class of materials formed by the self-assembly of organic ligands and metal ions, creating a network structure. The current investigation effectively achieves the loading [...] Read more.
Recently, researchers have employed metal–organic frameworks (MOFs) for loading pharmaceutically important substances. MOFs are a novel class of porous class of materials formed by the self-assembly of organic ligands and metal ions, creating a network structure. The current investigation effectively achieves the loading of adenosine (ADN) into a metal–organic framework based on cyclodextrin (CD) using a solvent diffusion method. The composite material, referred to as ADN:β-CD-K MOFs, is created by loading ADN into beta-cyclodextrin (β-CD) with the addition of K+ salts. This study delves into the detailed examination of the interaction between ADN and β-CD in the form of MOFs. The focus is primarily on investigating the hydrogen bonding interaction and energy parameters through the aid of semi-empirical quantum mechanical computations. The analysis of peaks that are associated with the ADN-loaded ICs (inclusion complexes) within the MOFs indicates that ADN becomes incorporated into a partially amorphous state. Observations from SEM images reveal well-defined crystalline structures within the MOFs. Interestingly, when ADN is absent from the MOFs, smaller and irregularly shaped crystals are formed. This could potentially be attributed to the MOF manufacturing process. Furthermore, this study explores the additional cross-linking of β-CD with K through the coupling of -OH on the β-CD-K MOFs. The findings corroborate the results obtained from FT-IR analysis, suggesting that β-CD plays a crucial role as a seed in the creation of β-CD-K MOFs. Furthermore, the cytotoxicity of the MOFs is assessed in vitro using MDA-MB-231 cells (human breast cancer cells). Full article
(This article belongs to the Special Issue Molecular Targets for Breast Cancer Therapy)
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Review

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29 pages, 2370 KiB  
Review
Targeting Breast Cancer: The Familiar, the Emerging, and the Uncharted Territories
by Hamidreza Montazeri Aliabadi, Arthur Manda, Riya Sidgal and Co Chung
Biomolecules 2023, 13(9), 1306; https://doi.org/10.3390/biom13091306 - 25 Aug 2023
Cited by 2 | Viewed by 1823
Abstract
Breast cancer became the most diagnosed cancer in the world in 2020. Chemotherapy is still the leading clinical strategy in breast cancer treatment, followed by hormone therapy (mostly used in hormone receptor-positive types). However, with our ever-expanding knowledge of signaling pathways in cancer [...] Read more.
Breast cancer became the most diagnosed cancer in the world in 2020. Chemotherapy is still the leading clinical strategy in breast cancer treatment, followed by hormone therapy (mostly used in hormone receptor-positive types). However, with our ever-expanding knowledge of signaling pathways in cancer biology, new molecular targets are identified for potential novel molecularly targeted drugs in breast cancer treatment. While this has resulted in the approval of a few molecularly targeted drugs by the FDA (including drugs targeting immune checkpoints), a wide array of signaling pathways seem to be still underexplored. Also, while combinatorial treatments have become common practice in clinics, the majority of these approaches seem to combine molecularly targeted drugs with chemotherapeutic agents. In this manuscript, we start by analyzing the list of FDA-approved molecularly targeted drugs for breast cancer to evaluate where molecular targeting stands in breast cancer treatment today. We will then provide an overview of other options currently under clinical trial or being investigated in pre-clinical studies. Full article
(This article belongs to the Special Issue Molecular Targets for Breast Cancer Therapy)
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20 pages, 938 KiB  
Review
Challenges and Opportunities in Developing Targeted Therapies for Triple Negative Breast Cancer
by Abygail G. Chapdelaine and Gongqin Sun
Biomolecules 2023, 13(8), 1207; https://doi.org/10.3390/biom13081207 - 01 Aug 2023
Cited by 7 | Viewed by 2370
Abstract
Triple negative breast cancer (TNBC) is a heterogeneous group of breast cancers characterized by their lack of estrogen receptors, progesterone receptors, and the HER2 receptor. They are more aggressive than other breast cancer subtypes, with a higher mean tumor size, higher tumor grade, [...] Read more.
Triple negative breast cancer (TNBC) is a heterogeneous group of breast cancers characterized by their lack of estrogen receptors, progesterone receptors, and the HER2 receptor. They are more aggressive than other breast cancer subtypes, with a higher mean tumor size, higher tumor grade, the worst five-year overall survival, and the highest rates of recurrence and metastasis. Developing targeted therapies for TNBC has been a major challenge due to its heterogeneity, and its treatment still largely relies on surgery, radiation therapy, and chemotherapy. In this review article, we review the efforts in developing targeted therapies for TNBC, discuss insights gained from these efforts, and highlight potential opportunities going forward. Accumulating evidence supports TNBCs as multi-driver cancers, in which multiple oncogenic drivers promote cell proliferation and survival. In such multi-driver cancers, targeted therapies would require drug combinations that simultaneously block multiple oncogenic drivers. A strategy designed to generate mechanism-based combination targeted therapies for TNBC is discussed. Full article
(This article belongs to the Special Issue Molecular Targets for Breast Cancer Therapy)
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