Mehta Kasshish, Hegde Mangala, Girisa Sosmitha, Vishwa Ravichandran, Alqahtani Mohammed S, Abbas Mohamed, Shakibaei Mehdi, Sethi Gautam, Kunnumakkara Ajaikumar B
Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati (IITG), Guwahati, Assam, 781039, India.
Radiological Sciences Department, College of Applied Medical Sciences, King Khalid University, 61421, Abha, Saudi Arabia.
Mil Med Res. 2024 Dec 12;11(1):76. doi: 10.1186/s40779-024-00582-z.
The extensive heterogeneity and the limited availability of effective targeted therapies contribute to the challenging prognosis and restricted survival observed in triple-negative breast cancer (TNBC). Recent research indicates the aberrant expression of diverse tyrosine kinases (TKs) within this cancer, contributing significantly to tumor cell proliferation, survival, invasion, and migration. The contemporary paradigm shift towards precision medicine has highlighted TKs and their receptors as promising targets for pharmacotherapy against a range of malignancies, given their pivotal roles in tumor initiation, progression, and advancement. Intensive investigations have focused on various monoclonal antibodies (mAbs) and small molecule inhibitors that specifically target proteins such as epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor (VEGFR), cellular mesenchymal-epithelial transition factor (c-MET), human epidermal growth factor receptor 2 (HER2), among others, for combating TNBC. These agents have been studied both in monotherapy and in combination with other chemotherapeutic agents. Despite these advances, a substantial terrain of unexplored potential lies within the realm of TK targeted therapeutics, which hold promise in reshaping the therapeutic landscape. This review summarizes the various TK targeted therapeutics that have undergone scrutiny as potential therapeutic interventions for TNBC, dissecting the outcomes and revelations stemming from diverse clinical investigations. A key conclusion from the umbrella clinical trials evidences the necessity for in-depth molecular characterization of TNBCs for the maximum efficiency of TK targeted therapeutics, either as standalone treatments or a combination. Moreover, our observation highlights that the outcomes of TK targeted therapeutics in TNBC are substantially influenced by the diversity of the patient cohort, emphasizing the prioritization of individual patient genetic/molecular profiles for precise TNBC patient stratification for clinical studies.
三阴性乳腺癌（TNBC）预后具有挑战性且生存期受限，这是由其广泛的异质性和有效靶向治疗的有限可用性导致的。最近的研究表明，这种癌症中多种酪氨酸激酶（TKs）表达异常，这对肿瘤细胞的增殖、存活、侵袭和迁移有显著影响。鉴于TKs及其受体在肿瘤发生、发展和进展中起关键作用，当代向精准医学的范式转变突出了它们作为针对一系列恶性肿瘤的药物治疗的有前景靶点。深入研究集中在各种单克隆抗体（mAbs）和小分子抑制剂上，这些药物特异性靶向表皮生长因子受体（EGFR）、血管内皮生长因子（VEGF）、血管内皮生长因子受体（VEGFR）、细胞间充质-上皮转化因子（c-MET）、人表皮生长因子受体2（HER2）等蛋白质，用于对抗TNBC。这些药物已在单药治疗以及与其他化疗药物联合使用中进行了研究。尽管有这些进展，但在TK靶向治疗领域仍有大量未被探索的潜力，有望重塑治疗格局。本综述总结了各种作为TNBC潜在治疗干预措施而受到审查的TK靶向治疗方法，剖析了不同临床研究的结果和启示。伞式临床试验的一个关键结论证明，为了使TK靶向治疗达到最大效率，无论是作为单一治疗还是联合治疗，都需要对TNBC进行深入的分子特征分析。此外，我们的观察结果强调，TNBC中TK靶向治疗的结果受患者群体多样性的显著影响，这突出了在临床研究中为精确的TNBC患者分层而优先考虑个体患者的基因/分子谱的重要性。
