De-Escalating Treatment Strategies for Patients with Human Epidermal Growth Factor Receptor-2 (HER2)-Positive Early-Stage Breast Cancer DOI Open Access
Hikmat Abdel‐Razeq

Cancers, Journal Year: 2024, Volume and Issue: 16(20), P. 3478 - 3478

Published: Oct. 14, 2024

Almost one-fifth of breast cancer cases express Human Epidermal Growth Factor-2 (HER2), and such expression is associated with highly proliferative tumors poor prognosis. The introduction anti-HER2 therapies has dramatically changed the natural course this aggressive subtype cancer. However, therapy can be substantial toxicities, mostly cardiac, high cost. Over past few years, there been growing interest in de-escalation to minimize adverse events healthcare costs, while maintaining efficacy treatment. Data from clinical observations single-arm studies have eluted minimal impact low-risk patients, like those node-negative small tumors. Though single-arm, APT trial, which patients node-negative, received single-agent paclitaxel for 12 cycles plus trastuzumab 1 year, was a practice-changing study. Several other recently published studies, PERSEPHONE shown more convincing data that 6 months not inferior months, terms disease-free survival (DFS), suggesting de-escalating strategies shorter treatment may appropriate some patients. Other involved an adaptive, response-directed approach, personalized depends on tumor genomic profiling.

Language: Английский

LMAN2 interacts with HEATR3 to expedite HER2-positive breast cancer advancement and inflammation and Akt/ERK/NF-κB signaling DOI

Sujian Xiao,

Tong Yu, Fulan Yang

et al.

Biochemistry and Cell Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

The paper aimed to reveal the impacts and possible mechanism of action lectin mannose-binding 2 protein (LMAN2) in HER2-positive breast cancer (BC). expression, prognostic potential LMAN2, correlation between LMAN2 HEAT repeat containing 3 (HEATR3) BC were analyzed TCGA database. Intact, Mentha, BioGrid databases predicted LMAN2–HEATR3 interactions. Reverse transcription-quantitative PCR Western blot examined expression. Cell Counting Kit-8, 5-ethynyl-2′-deoxyuridine staining, wound healing, transwell assays, respectively, detected aggressive cellular biological behaviors including proliferation, migration, invasion. expression matrix metalloproteinases, HEATR3, kinase B (Akt)/extracellular signal-regulated (ERK)/nuclear factor-kappaB (NF-κB) signaling-related proteins. Co-immunoprecipitation assay was used prove relationship with HEATR3. Enzyme-linked immunosorbent inflammatory cytokine levels. overexpressed tissues cells indicated unfavorable prognosis patients. knockdown suppressed cell interacted had a positive HEATR3 up-regulation reversed repressive role interference progression BC, Akt/ERK/NF-κB signaling, response. Altogether, silencing might exert anti-tumor anti-inflammatory properties inactivate signaling via binding

Language: Английский

Citations

1
HER2-positive gastric cancer: from targeted therapy to CAR-T cell therapy DOI Creative Commons
Qiang Shao,

Junge Deng,

Haoran Wu

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 13, 2025

Gastric cancer (GC) ranks as the fifth most prevalent on a global scale, with HER2-positive GC representing distinct subtype that exhibits more intricate biological characteristics. Conventional chemotherapy typically restricted efficacy in management of GC. In light incessant advancement molecular targeted therapies, targeting HER2 has emerged promising therapeutic approach for this subtype. The advent antibody-drug conjugates (ADCs) and chimeric antigen receptor T-cell therapy (CAR-T) furnished novel treatment alternatives Nevertheless, owing to pronounced heterogeneity complex tumor microenvironment, drug resistance frequently emerges, thereby substantially influencing effectiveness HER2-targeted therapy. This article comprehensively summarizes deliberates upon strategies well underlying mechanisms.

Language: Английский

Citations

1
Ultrasound-Guided Histotripsy Triggers the Release of Tumor-Associated Antigens from Breast Cancers DOI Open Access

Shengzhuang Tang,

Reliza McGinnis,

Zhengyi Cao

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(2), P. 183 - 183

Published: Jan. 8, 2025

Background/Objectives: There is increasing evidence to indicate that histotripsy treatment can enhance the host anti-tumor immune responses both locally at targeting tumor site as well systemically from abscopal effects. Histotripsy a non-invasive ultrasound ablation technology mechanically disrupts target tissue via cavitation. A key factor contributing histotripsy-induced effects believed be release of tumor-specific antigens (TSAs) or tumor-associated (TAAs) induce systemic response. In this study, we studied effect on HER2, well-defined TAA for cancer immunotherapy. Methods: range doses administered HER2-postive mammary cells in an vitro cell culture system and ex vivo were applied. addition, single dose was used murine model. The released proteins, specifically cell-free supernatants pellets analyzed by BCA protein assay, ultra-performance liquid chromatography (UPLC) Western blot. Results: Our results showed could significantly trigger HER2 proteins current study. level actually higher than pellets, suggesting intracellular domain into extracellular compartment. Furthermore, proportionally more doses, indicating free histotripsy-dose-dependent. Conclusions: conclusion, have qualitatively quantitatively demonstrated triggers histotripsy-mediated provides important insights mechanism underlying its immunostimulation suggests potential TSA/TAA-based immunotherapies numerous types.

Language: Английский

Citations

0
Adipokines in Breast Cancer: Decoding Genetic and Proteomic Mechanisms Underlying Migration, Invasion, and Proliferation DOI Creative Commons

Anne Ließem,

Uwe Leimer,

Günter Germann

et al.

Breast Cancer Targets and Therapy, Journal Year: 2025, Volume and Issue: Volume 17, P. 79 - 102

Published: Jan. 1, 2025

Adipokines, bioactive peptides secreted by adipose tissue, appear to contribute breast cancer development and progression. While numerous studies suggest their role in promoting tumor growth, the exact mechanisms of involvement are not yet completely understood. In this project, varying concentrations recombinant human adipokines (Leptin, Lipocalin-2, PAI-1, Resistin) were used study effects on four selected cell lines (EVSA-T, MCF-7, MDA-MB-231, SK-Br-3). Over a five-day proliferation phase, linear growth was assessed calculating doubling times malignancy-associated changes gene protein expression identified using quantitative TaqMan real-time PCR multiplex analysis. Migration invasion behaviors quantified specialized Boyden chamber assays. We found significant, adipokine-mediated genetic proteomic alterations, with showing an up 6-fold increase genes after adipokine-supplementation. Adipokines further altered secretion, such as raising different tumor-associated proteins 13-fold. Effects varied, however, most approaches significant enhancement kinetics. A concentration-dependent migration generally observed, no reductions any approaches. could show robust effect several cells vitro. Understanding interaction between tissue opens potential avenues for innovative prevention therapy strategies. Our findings indicate that antibodies against specific become beneficial component clinical treatment future.

Language: Английский

Citations

0
Research Progress on PI3K/AKT/mTOR Signaling Pathway and Multidrug Resistance in Breast Cancer DOI

鸿艳 陈

Hans Journal of Biomedicine, Journal Year: 2025, Volume and Issue: 15(02), P. 328 - 338

Published: Jan. 1, 2025

Language: Английский

Citations

0
Paclitaxel Resistance in Breast Cancer: Current Challenges and Recent Advanced Therapeutic Strategies DOI Creative Commons

Heidi A Abouzeid,

Loay Kassem, Xumei Liu

et al.

Cancer Treatment and Research Communications, Journal Year: 2025, Volume and Issue: unknown, P. 100918 - 100918

Published: March 1, 2025

Breast cancer (BC) is one of the leading causes cancer-related deaths among women worldwide. Paclitaxel (PTX), a chemotherapeutic agent derived from taxane family, commonly used in treating BC due to its ability disrupt microtubule dynamics and induce cell death. However, resistance PTX presents significant challenge, as it diminishes drug's effectiveness can lead treatment failure. This review explores mechanisms by which exerts effects various factors contributing resistance. These include genetic mutations that affect tubulin dynamics, role non-coding RNAs, molecular pathways involved chemoresistance, epigenetic changes, post-transcriptional modifications, increased activity ABC transporters promote drug efflux, immunosuppressive interactions within tumor microenvironment, mediated autophagy. also strategies overcome resistance, including innovations, combination therapies, nanotechnology-based approaches. may improve efficacy enhance outcomes for patients.

Language: Английский

Citations

0
Navigating the future of gastric cancer treatment: a review on the impact of antibody-drug conjugates DOI Creative Commons
Qian-Qing Yin, Yanlong Zhang,

Xueqing Xie

et al.

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: April 5, 2025

Abstract Gastric cancer, marked by its high incidence and poor prognosis, demands the urgent development of novel effective treatment strategies, especially for patients ineligible surgery or those who have had limited success with chemotherapy, radiotherapy targeted therapies. Recently, antibody-drug conjugates (ADCs) become a key area investigation due to their specificity potent antitumor effects. These therapies combine monoclonal antibodies, designed bind tumor-specific antigens, cytotoxic agents that selectively target destroy malignant cells. ADCs generated significant interest in clinical trials as promising approach improve both efficacy patient outcomes gastric cancer. However, application is not without challenges limitations must be addressed. This review discusses recent progress use cancer treatment.

Language: Английский

Citations

0
A Comprehensive Review About the Use of Monoclonal Antibodies in Cancer Therapy DOI Creative Commons
Angel A Justiz-Vaillant, Bijay Raj Pandit, Chandrashekhar Unakal

et al.

Antibodies, Journal Year: 2025, Volume and Issue: 14(2), P. 35 - 35

Published: April 11, 2025

Monoclonal antibodies (mAbs) targeting various pathways in cancer therapy play crucial roles enhancing the immune system's ability to recognise and eliminate tumour cells. These therapies are designed either block inhibitory checkpoint or target specific cell markers for direct destruction. Additionally, mAbs can modulate microenvironment, enhance antibody-dependent cellular cytotoxicity, inhibit angiogenesis, further amplifying their therapeutic impact. Below is a summary of monoclonal key pathways, along with indications mechanisms action, which reviewed based on mechanisms.

Language: Английский

Citations

0
Biomarker validation: challenges and regulatory perspectives DOI
Bindiya Chauhan, Bhuvnesh Kumar Singh,

Tuhin James Paul

et al.

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 149 - 176

Published: Jan. 1, 2025

Language: Английский

Citations

0
Insights into the molecular and genetic role of obesity in breast cancer pathogenesis DOI Creative Commons
Sandeep Mallya,

V. Gangadhar,

Sophia Evangeline Aldrin

et al.

Cancer Biology & Therapy, Journal Year: 2025, Volume and Issue: 26(1)

Published: May 12, 2025

The epidemic of obesity is a growing concern and one the major risk factors for several chronic diseases, including types cancers. correlation breast cancer with has been extensively studied involves an interplay hormonal, metabolic, genetic explored in this review. Inflammation hormone dysregulation play important role promoting protumorigenic environment through adipose tissue, which involved energy storage functions as endocrine organ. As result, various cytokines, primarily proinflammatory nature, are released, resulting low-grade inflammation tumor growth. Additionally, obese conditions also induce imbalances hormones, particularly estrogen insulin, both drive carcinogenesis. Genetic components such single nucleotide polymorphisms critical roles modulating between cancer. This review provides comprehensive overview mechanisms underlying incidence progression.

Language: Английский

Citations

0