{"title":"Synergistic Targeting of EGFR, ESR1, BCL2, and TP53 Pathways: A Multi-Pronged Approach for Advanced Breast Cancer Therapy.","authors":"Harneet Marwah, Hitesh Kumar Dewangan","doi":"10.2174/0115680096366956250314043513","DOIUrl":null,"url":null,"abstract":"<p><p>Breast cancer is a heterogeneous disease driven by complex molecular signaling pathways that influence tumor progression, metastasis, and treatment resistance. This review provides a comprehensive analysis of the molecular mechanisms underlying breast cancer, with a focus on key pathways such as EGFR, ESR1, BCL2, and TP53. We examine the roles of these pathways in regulating critical cellular processes, including proliferation, survival, apoptosis, and migration. EGFR's involvement in cell proliferation and migration, as well as its overexpression and mutations in breast cancer, are discussed, alongside the impact of ESR1 signaling in hormone-receptor-positive breast cancer and resistance to endocrine ther-apies. Additionally, the review highlights the function of BCL2 in apoptosis regulation and its overexpression in conferring resistance while also exploring the role of TP53 in cell cycle control and apoptosis, particularly its mutations that contribute to poor prognosis. Further-more, the interplay between these molecular pathways-such as the crosstalk between EGFR and ESR1, BCL2-TP53 interactions, and the EGFR-TP53 mutational relationships-illustrates the complexity of resistance mechanisms and the need for multi-targeted thera-peutic strategies. The concept of synergistic targeting, including the integration of the PI3K/AKT/mTOR pathway, is explored, with evidence supporting the potential for over-coming resistance and improving therapeutic outcomes. We also discuss the emerging role of personalized medicine, emphasizing biomarker-driven approaches for patient selection and tailored treatments. Finally, advancements in nanoparticle-based drug delivery systems are reviewed, addressing their potential to enhance therapeutic efficacy and address current challenges in cancer therapy. This review highlights the critical importance of understanding the molecular underpinnings of breast cancer and the need for integrated, multi-targeted ap-proaches to overcome therapeutic resistance, offering insights into future directions for im-proving clinical outcomes in breast cancer treatment.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.3000,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current cancer drug targets","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0115680096366956250314043513","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Breast cancer is a heterogeneous disease driven by complex molecular signaling pathways that influence tumor progression, metastasis, and treatment resistance. This review provides a comprehensive analysis of the molecular mechanisms underlying breast cancer, with a focus on key pathways such as EGFR, ESR1, BCL2, and TP53. We examine the roles of these pathways in regulating critical cellular processes, including proliferation, survival, apoptosis, and migration. EGFR's involvement in cell proliferation and migration, as well as its overexpression and mutations in breast cancer, are discussed, alongside the impact of ESR1 signaling in hormone-receptor-positive breast cancer and resistance to endocrine ther-apies. Additionally, the review highlights the function of BCL2 in apoptosis regulation and its overexpression in conferring resistance while also exploring the role of TP53 in cell cycle control and apoptosis, particularly its mutations that contribute to poor prognosis. Further-more, the interplay between these molecular pathways-such as the crosstalk between EGFR and ESR1, BCL2-TP53 interactions, and the EGFR-TP53 mutational relationships-illustrates the complexity of resistance mechanisms and the need for multi-targeted thera-peutic strategies. The concept of synergistic targeting, including the integration of the PI3K/AKT/mTOR pathway, is explored, with evidence supporting the potential for over-coming resistance and improving therapeutic outcomes. We also discuss the emerging role of personalized medicine, emphasizing biomarker-driven approaches for patient selection and tailored treatments. Finally, advancements in nanoparticle-based drug delivery systems are reviewed, addressing their potential to enhance therapeutic efficacy and address current challenges in cancer therapy. This review highlights the critical importance of understanding the molecular underpinnings of breast cancer and the need for integrated, multi-targeted ap-proaches to overcome therapeutic resistance, offering insights into future directions for im-proving clinical outcomes in breast cancer treatment.
期刊介绍:
Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes and genes.
Current Cancer Drug Targets publishes original research articles, letters, reviews / mini-reviews, drug clinical trial studies and guest edited thematic issues written by leaders in the field covering a range of current topics on drug targets involved in cancer.
As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.