Varshini Magham Sai, Krishnamurthy Praveen Thaggikuppe, Reddy Ramakamma Aishwarya, Wadhwani Ashish, Chandrashekar V M
Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty, 643001, TN, India.
Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty, 643001, TN, India.
Curr Cancer Drug Targets. 2025;25(1):3-25. doi: 10.2174/0115680096280750240123054936.
Triple-negative Breast Cancer (TNBC), the most aggressive breast cancer subtype, is characterized by the non-appearance of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Clinically, TNBC is marked by its low survival rate, poor therapeutic outcomes, high aggressiveness, and lack of targeted therapies. Over the past few decades, many clinical trials have been ongoing for targeted therapies in TNBC. Although some classes, such as Poly (ADP Ribose) Polymerase (PARP) inhibitors and immunotherapies, have shown positive therapeutic outcomes, however, clinical effects are not much satisfiable. Moreover, the development of drug resistance is the major pattern observed in many targeted monotherapies. The heterogeneity of TNBC might be the cause for limited clinical benefits. Hence,, there is a need for the potential identification of new therapeutic targets to address the above limitations. In this context, some novel targets that can address the above-mentioned concerns are emerging in the era of TNBC therapy, which include Hypoxia Inducible Factor (HIF-1α), Matrix Metalloproteinase 9 (MMP-9), Tumour Necrosis Factor-α (TNF-α), β-Adrenergic Receptor (β-AR), Voltage Gated Sodium Channels (VGSCs), and Cell Cycle Regulators. Currently, we summarize the ongoing clinical trials and discuss the novel therapeutic targets in the management of TNBC.
三阴性乳腺癌(TNBC)是最具侵袭性的乳腺癌亚型,其特征是不表达雌激素受体(ER)、孕激素受体(PR)和人表皮生长因子受体2(HER2)。临床上,TNBC的特点是生存率低、治疗效果差、侵袭性高且缺乏靶向治疗。在过去几十年里,针对TNBC的靶向治疗进行了许多临床试验。尽管有些类别,如聚(ADP核糖)聚合酶(PARP)抑制剂和免疫疗法,已显示出积极的治疗效果,然而,临床效果并不十分令人满意。此外,耐药性的产生是许多靶向单一疗法中观察到的主要模式。TNBC的异质性可能是临床获益有限的原因。因此,需要潜在地确定新的治疗靶点以解决上述局限性。在此背景下,在TNBC治疗时代出现了一些能够解决上述问题的新靶点,包括缺氧诱导因子(HIF-1α)、基质金属蛋白酶9(MMP-9)、肿瘤坏死因子-α(TNF-α)、β-肾上腺素能受体(β-AR)、电压门控钠通道(VGSCs)和细胞周期调节剂。目前,我们总结了正在进行的临床试验,并讨论了TNBC治疗中的新治疗靶点。