Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
8.0
4.5
Journals
Cancers
Special Issues
New Insights into Targeted Drugs for Breast Cancer (Volume II)
share announcement

New Insights into Targeted Drugs for Breast Cancer (Volume II)

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

Deadline for manuscript submissions: 1 July 2025 | Viewed by 6008

Special Issue Editors

Dr. Jennifer Diamond

E-Mail Website
Guest Editor
University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, 12801 E 17th Ave, MS8117, Aurora, CO 80045, USA
Interests: triple-negative breast cancer; phase I clinical trials; drug resistance
Special Issues, Collections and Topics in MDPI journals
Dr. Jennifer Richer

E-Mail Website
Guest Editor
Department of Pathology, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA
Interests: hormone receptor-positive breast cancer; androgen receptor inhibitors in breast cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is the second edition of the Special Issue, "New Insights into Targeted Drugs for Breast Cancer" (https://www.mdpi.com/journal/cancers/special_issues/TDBC).

Over the last decade we have seen a rapid increase in targeted therapies for breast cancer, including in hormone receptor (HR)-positive, HER2+ and triple-negative breast cancer (TNBC). The development of CDK4/6, PI3K and new SERDs in HR+ breast cancer, new HER2-targeted therapies (including small-molecule inhibitors, ADCs and monoclonal antibodies), and Trop2-ADCs and PARP inhibitors for TNBC and BRCA-mutated cancers, respectively, have changed the way we treat patients with all breast cancer subtypes. These advances have improved patient outcomes and given clinicians more treatment options.

For this Special Issue of Cancers, we welcome original and review papers focused on targeted therapies in breast cancer, including novel rational combinations and strategies to overcome treatment resistance.  While this Special Issue is not focused on immunotherapy, works focused on combination strategies including immunotherapy and targeted therapies are also encouraged.

Dr. Jennifer Diamond
Dr. Jennifer Richer
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
  • targeted therapies
  • treatment resistance
  • HER2
  • hormone receptor-positive
  • triple-negative breast cancer

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • Reprint: MDPI Books provides the opportunity to republish successful Special Issues in book format, both online and in print.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (4 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

16 pages, 3142 KiB  
Article
Effect of Tasurgratinib as an Orally Available FGFR1–3 Inhibitor on Resistance to a CDK4/6 Inhibitor and Endocrine Therapy in ER+/HER2− Breast Cancer Preclinical Models
by Satoshi Kawano, Sayo Fukushima, Kyoko Nishibata, Ryu Gejima and Saori Watanabe Miyano
Cancers 2025, 17(7), 1084; https://doi.org/10.3390/cancers17071084 - 24 Mar 2025
Viewed by 486
Abstract
Background: Fibroblast growth factor (FGF) signaling plays a crucial role in several cellular functions in cancer cells. Tasurgratinib, formerly known as E7090, is an orally available FGF receptor (FGFR)1–3 selective inhibitor. Here, we present the effects of tasurgratinib on the resistance to CDK4/6 [...] Read more.
Background: Fibroblast growth factor (FGF) signaling plays a crucial role in several cellular functions in cancer cells. Tasurgratinib, formerly known as E7090, is an orally available FGF receptor (FGFR)1–3 selective inhibitor. Here, we present the effects of tasurgratinib on the resistance to CDK4/6 inhibitors and endocrine therapy (ET) in a preclinical model. Methods: Estrogen receptor (ER)+ breast cancer (BC) patient-derived xenograft (PDX) models harboring ESR1 wild-type or ESR1 mutation were used as animal models. An in vitro cell proliferation assay of ER+ BC cell lines treated with fulvestrant or palbociclib + fulvestrant was conducted in the presence of FGF2 and FGF10, with or without tasurgratinib. Results: Among five ER+ BC PDX models, OD-BRE-0438 and OD-BRE-0704 showed higher sensitivities to tasurgratinib with prior palbociclib + fulvestrant than without it. In these models, palbociclib + fulvestrant treatment upregulated the expression of several FGF ligand mRNAs. In vitro, FGF2 and FGF10 decreased the sensitivity to both fulvestrant and palbociclib + fulvestrant, which was restored by co-treatment with tasurgratinib. Consistently, fulvestrant + tasurgratinib and elacestrant + tasurgratinib showed antitumor activity in ER+ BC PDX models harboring ESR1 wild-type and ESR1 mutation, respectively. In these models, fulvestrant or elacestrant upregulated the expression of several FGF ligand mRNAs. Conclusions: FGF signaling plays a role in resistance to CDK4/6 inhibitors and ET in ER+ BC. Tasurgratinib has the potential to exhibit significant antitumor activity in combination with ET against ER+ BC via FGF signaling inhibition. These findings indicate the therapeutic potential of tasurgratinib in treating ER+ BC. Full article
(This article belongs to the Special Issue New Insights into Targeted Drugs for Breast Cancer (Volume II))
►▼ Show Figures

Figure 1

13 pages, 1620 KiB  
Article
Real-World Efficacy and Adherence to Palbociclib in HR-Positive, HER2-Negative Advanced Breast Cancer: Insights from a Romanian Cohort
by Cristian Virgil Lungulescu, Georgiana-Cristiana Camen, Mihaela-Simona Naidin, Tradian-Ciprian Berisha, Andrei Bita, Venera-Cristina Dinescu, Sandra Alice Buteica, Marina-Daniela Dimulescu, Simona Ruxandra Volovat and Adina Turcu-Stiolica
Cancers 2024, 16(24), 4161; https://doi.org/10.3390/cancers16244161 - 13 Dec 2024
Viewed by 1075
Abstract
Background/Objectives: The first reimbursed prescription for palbociclib (Palbo) in breast cancer patients in Romania was issued in July 2018. The objective of this study is to assess the efficacy, safety, and adherence to Palbo in combination with aromatase inhibitor (AI) or fulvestrant in [...] Read more.
Background/Objectives: The first reimbursed prescription for palbociclib (Palbo) in breast cancer patients in Romania was issued in July 2018. The objective of this study is to assess the efficacy, safety, and adherence to Palbo in combination with aromatase inhibitor (AI) or fulvestrant in a real-world cohort of HR+/HER2− breast cancer patients from Romania. Methods: A retrospective analysis of reimbursed Palbo prescriptions was conducted using data extracted from the electronic database of the Romanian Health Insurance House, Dolj County, for disease code 124 (breast cancer), covering the period from 2018 to 2023. The primary outcome assessed was time to treatment discontinuation (TTD), with secondary outcomes including overall survival (OS) and Palbo adherence (which was measured by medication possession ratio). Results: A total of 125 patients were identified, with a median age of 62 years (IQR, 53–70), and 98% were female. Two treatment combinations were observed: Palbo + Aromatase Inhibitor (AI) in 104 patients (83.2%) and Palbo + fulvestrant in 21 patients (16.8%). The median TTD for the entire cohort was 19 months (95%CI, 19.3–24.9 months). In patients treated with Palbo + AI, the median TTD was not available/reached [NA] (95%CI, 36.0-NA months). For those receiving Palbo+fulvestrant, the median TTD was 25.0 months (95%CI, 13.0-NR months). No significant differences in TTD were observed among the two treatment combinations (χ2 = 1.33, df = 1, log-rank p = 0.249). The 12- and 36-month TTD rates were higher for Palbl combined with AI than combined with fulvestrant: 77.8% [95%CI, 69.7–86.7%] vs. 71.8% [95%CI, 53.6–96.2%], and 56.3% [95%CI, 45.9–69%] vs. 49.7% [95%CI, 29.7–83.2%], respectively. The median OS was 38 months (95%CI, 25.5–50.9). When treatment involved Palbo + AI, the median OS was NA (95%CI, 54.8-NA) months. When treatment involved Palbo + fulvestrant, the median was 50.8 (95%CI, 34.1-NA) months. Related to OS, no significant differences were found between the two types of treatments (log-rank p = 0.638). The 24- and 36-month OS rates were higher for Palbo combined with AI than combined with fulvestrant: 76.9% [95%CI, 69.2–85.5%] vs. 81% [95%CI, 65.8–99.6%], and 67.9% [95%CI, 59.2–77.8%] vs. 65.3% [95%CI, 47.4–90.0%], respectively. The mean adherence in our study was 0.91 ± 0.1. We found no correlation between adherence to Palbo and OS (Spearman’s rho = 0.04, p = 0.593). Conclusions: While both AI and fulvestrant remain viable options, the lack of significant differences in survival between these combinations suggests that treatment choice can be tailored to individual patient needs. Full article
(This article belongs to the Special Issue New Insights into Targeted Drugs for Breast Cancer (Volume II))
►▼ Show Figures

Figure 1

15 pages, 4785 KiB  
Article
Mechanism of miRNAs and miRNA-mRNA Regulatory Networks in Modulating Drug Resistance in HER2-Positive Breast Cancer: An Integrative Bioinformatics Approach
by Thanh Hoa Vo, Edel A. McNeela, Orla O’Donovan, Sweta Rani and Jai Prakash Mehta
Cancers 2024, 16(23), 3962; https://doi.org/10.3390/cancers16233962 - 26 Nov 2024
Viewed by 1212
Abstract
Background: HER2-positive breast cancer is an aggressive subtype where innate/acquired resistance to targeted drugs remains a challenge. This study aims to uncover the underlying mechanisms of HER2 drug resistance through miRNA analysis and target identification. Methods: MiRNA datasets were systematically retrieved from the [...] Read more.
Background: HER2-positive breast cancer is an aggressive subtype where innate/acquired resistance to targeted drugs remains a challenge. This study aims to uncover the underlying mechanisms of HER2 drug resistance through miRNA analysis and target identification. Methods: MiRNA datasets were systematically retrieved from the GEO database, and differential expression analysis was conducted for both miRNA and mRNA datasets. Functional analyses were also conducted to validate the identified miRNAs and assess their clinical relevance. Results: We identified 113 differentially expressed miRNAs (DEMs) and 923 target genes. Validation was performed using external mRNA datasets, and intersection with significant genes identified 110 overlapping genes associated with HER2 drug resistance. Further analyses included functional enrichment, construction of a protein–protein interaction (PPI) network, identification of key hub genes such as BCL2, FOS, and CXCR4, and assessment of clinical relevance through survival analysis and immunohistochemistry (IHC) assessments. Conclusions: This integrative approach unveils a complex landscape of HER2 drug resistance in breast cancer, identifying crucial miRNAs, target genes, and significant pathways. The findings offer novel insights into the mechanisms governing drug resistance and highlight the potential for enhancing therapeutic strategies. Future studies are necessary for experimental validation to further explore the complex mechanisms involved. Full article
(This article belongs to the Special Issue New Insights into Targeted Drugs for Breast Cancer (Volume II))
►▼ Show Figures

Figure 1

25 pages, 5492 KiB  
Article
Molecular Atlas of HER2+ Breast Cancer Cells Treated with Endogenous Ligands: Temporal Insights into Mechanisms of Trastuzumab Resistance
by Kavitha Mukund, Jackelyn A. Alva-Ornelas, Adam L. Maddox, Divya Murali, Darya Veraksa, Andras Saftics, Jerneja Tomsic, David Frankhouser, Meagan Razo, Tijana Jovanovic-Talisman, Victoria L. Seewaldt and Shankar Subramaniam
Cancers 2024, 16(3), 553; https://doi.org/10.3390/cancers16030553 - 27 Jan 2024
Viewed by 2425
Abstract
Trastuzumab therapy in HER2+ breast cancer patients has mixed success owing to acquired resistance to therapy. A detailed understanding of downstream molecular cascades resulting from trastuzumab resistance is yet to emerge. In this study, we investigate the cellular mechanisms underlying acquired resistance using [...] Read more.
Trastuzumab therapy in HER2+ breast cancer patients has mixed success owing to acquired resistance to therapy. A detailed understanding of downstream molecular cascades resulting from trastuzumab resistance is yet to emerge. In this study, we investigate the cellular mechanisms underlying acquired resistance using trastuzumab-sensitive and -resistant cancer cells (BT474 and BT474R) treated with endogenous ligands EGF and HRG across time. We probe early receptor organization through microscopy and signaling events through multiomics measurements and assess the bioenergetic state through mitochondrial measurements. Integrative analyses of our measurements reveal significant alterations in EGF-treated BT474 HER2 membrane dynamics and robust downstream activation of PI3K/AKT/mTORC1 signaling. EGF-treated BT474R shows a sustained interferon-independent activation of the IRF1/STAT1 cascade, potentially contributing to trastuzumab resistance. Both cell lines exhibit temporally divergent metabolic demands and HIF1A-mediated stress responses. BT474R demonstrates inherently increased mitochondrial activity. HRG treatment in BT474R leads to a pronounced reduction in AR expression, affecting downstream lipid metabolism with implications for treatment response. Our results provide novel insights into mechanistic changes underlying ligand treatment in BT474 and BT474R and emphasize the pivotal role of endogenous ligands. These results can serve as a framework for furthering the understanding of trastuzumab resistance, with therapeutic implications for women with acquired resistance. Full article
(This article belongs to the Special Issue New Insights into Targeted Drugs for Breast Cancer (Volume II))
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-4
Back to TopTop