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靶向治疗与药物基因组学在个性化乳腺癌治疗中的进展:基因单核苷酸多态性在治疗耐药中的作用

Advancements in Targeted Therapies and Pharmacogenomics for Personalized Breast Cancer Treatment: The Role of Gene SNPs in Treatment Resistance.

作者信息

Tripathi Devika, Davies Neal M, Rajinikanth P S, Pandey Prashant

机构信息

Department of Pharmacy, PSIT-Pranveer Singh Institute of Technology (Pharmacy), Kanpur, India.

University of Alberta Faculty of Pharmacy and Pharmaceutical Sciences Edmonton, Canada.

出版信息

Curr Gene Ther. 2025 Jun 27. doi: 10.2174/0115665232373621250618181424.

Abstract

Breast cancer remains a prevalent and diverse disease, significantly contributing to cancer- related deaths among women worldwide. Recent advancements in molecular biology have paved the way for targeted therapies and pharmacogenomics, which are crucial for developing personalized treatment strategies. This literature review synthesizes findings from recent studies on these approaches, emphasizing clinical trials, genomic profiling, and personalized medicine. It aims to focus on studies examining targeted treatments, such as human epidermal growth factor receptor- 2 (HER2) inhibitors and CDK4/6 inhibitors, alongside pharmacogenomic data that influence drug metabolism, efficacy, and toxicity. Additionally, it examines the role of gene SNPs (Single Nucleotide Polymorphisms) correlated with treatment resistance, which have emerged as key biomarkers affecting therapeutic outcomes in breast cancer. These SNPs, found in genes involved in drug metabolism and tumor progression, contribute to variability in treatment responses and resistance in specific subtypes. They encompass various breast cancer subtypes, including hormone receptorpositive (HR+), HER2-positive, and triple-negative breast cancer (TNBC). The targeted therapies, particularly HER2 inhibitors, have markedly improved outcomes for specific subtypes. Furthermore, pharmacogenomics personalizes treatment by identifying genetic variations that affect drug response, optimizing therapy selection, and minimizing adverse effects. Despite these advancements, drug resistance remains a significant challenge, highlighting the necessity for ongoing research in molecular diagnostics and innovative therapeutic combinations. The literature suggests that precision medicine, driven by genomic profiling, pharmacogenomic data, and single nucleotide polymorphisms (SNPs) analysis, is enhancing treatment efficacy for breast cancer patients. HER2- positive and HR+ patients have especially benefitted from these targeted therapies while emerging treatments are addressing the complexities of TNBC. Additionally, genetic testing, such as BRCA1/2 mutation screening, is vital for guiding treatment decisions. Targeted therapies and pharmacogenomics have revolutionized breast cancer treatment, providing more personalized and effective care. Nevertheless, overcoming drug resistance and expanding access to genomic testing are essential for future advancements in this field.

摘要

乳腺癌仍然是一种普遍且多样的疾病,在全球女性癌症相关死亡中占很大比例。分子生物学的最新进展为靶向治疗和药物基因组学铺平了道路,这对于制定个性化治疗策略至关重要。这篇文献综述综合了近期关于这些方法的研究结果,重点关注临床试验、基因组分析和个性化医疗。其旨在聚焦于研究靶向治疗,如人表皮生长因子受体2(HER2)抑制剂和细胞周期蛋白依赖性激酶4/6(CDK4/6)抑制剂,以及影响药物代谢、疗效和毒性的药物基因组学数据。此外,它还研究了与治疗耐药性相关的基因单核苷酸多态性(SNP)的作用,这些SNP已成为影响乳腺癌治疗结果的关键生物标志物。这些SNP存在于参与药物代谢和肿瘤进展的基因中,导致特定亚型的治疗反应和耐药性存在差异。它们涵盖了各种乳腺癌亚型,包括激素受体阳性(HR+)、HER2阳性和三阴性乳腺癌(TNBC)。靶向治疗,尤其是HER2抑制剂,显著改善了特定亚型的治疗结果。此外,药物基因组学通过识别影响药物反应的基因变异来实现个性化治疗,优化治疗选择并最小化不良反应。尽管有这些进展,但耐药性仍然是一个重大挑战,凸显了在分子诊断和创新治疗组合方面持续研究的必要性。文献表明,由基因组分析、药物基因组学数据和单核苷酸多态性(SNP)分析驱动的精准医学正在提高乳腺癌患者的治疗效果。HER2阳性和HR+患者尤其受益于这些靶向治疗,而新兴治疗方法正在应对TNBC的复杂性。此外,基因检测,如BRCA1/2突变筛查,对于指导治疗决策至关重要。靶向治疗和药物基因组学彻底改变了乳腺癌治疗,提供了更个性化和有效的护理。然而,克服耐药性和扩大基因检测的可及性对于该领域未来的进展至关重要。

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