Breast cancer is the most frequently diagnosed cancer in women worldwide. Identifying reliable biomarkers and druggable molecular targets pose to be a significant quest in breast cancer research. p21-activated kinase 1 (PAK1) is a serine/threonine kinase that direct cell motility, cytoskeletal remodelling, and has been shown to function as a downstream regulator for various cancer signalling cascades that promote cell proliferation, apoptosis deregulation and hasten mitotic abnormalities, resulting in tumor formation and progression. The heterogeneity and acquired drug resistance are important factors that challenge the treatment of breast cancer. p21-activated kinase 1 signalling is crucial for activation of the Ras/RAF/MEK/ERK, PI3K/Akt/mTOR and Wnt signalling cascades which regulate cell survival, cell cycle progression, differentiation, and proliferation. A study involving proteogenomics analysis on breast cancer tissues showed the PAK1 as outlier kinase. In addition to this, few outlier molecules were identified specific to subtypes of breast cancer. A few substrates of PAK1 in breast cancer are already known. In this paper, we have discussed a similar approach called Kinase Interacting Substrate Screening (KISS) for the identification of novel oncogenic substrates of p21-activated kinase specific to subtypes of breast cancer. Such high throughput approaches are expected to accelerate the process of identifying novel drug targets and biomarkers.

乳腺癌是全世界女性中最常被诊断出的癌症。在乳腺癌研究中，确定可靠的生物标志物和可治疗的分子靶标是一项重要的任务。p21激活激酶1（PAK1）是一种丝氨酸/苏氨酸激酶，可指导细胞运动，细胞骨架重塑，并已显示出可作为多种癌症信号级联反应的下游调节剂，从而促进细胞增殖，凋亡失调并加速有丝分裂异常。在肿瘤的形成和发展中。异质性和获得性耐药性是挑战乳腺癌治疗的重要因素。p21激活的激酶1信号对于Ras / RAF / MEK / ERK，PI3K / Akt / mTOR和Wnt信号级联的激活至关重要，这些信号级联调节细胞存活，细胞周期进程，分化，和扩散。一项涉及对乳腺癌组织进行蛋白质组学分析的研究表明，PAK1是离群激酶。除此之外，几乎没有发现特定于乳腺癌亚型的异常分子。乳腺癌中PAK1的一些底物是已知的。在本文中，我们讨论了一种称为激酶相互作用底物筛选（KISS）的类似方法，用于鉴定对乳腺癌亚型具有特异性的p21活化激酶的新型致癌底物。预期这种高通量方法将加速鉴定新型药物靶标和生物标记物的过程。乳腺癌中PAK1的一些底物是已知的。在本文中，我们讨论了一种称为激酶相互作用底物筛选（KISS）的类似方法，用于鉴定对乳腺癌亚型具有特异性的p21活化激酶的新型致癌底物。预期这种高通量方法将加速鉴定新型药物靶标和生物标记物的过程。乳腺癌中PAK1的一些底物是已知的。在本文中，我们讨论了一种称为激酶相互作用底物筛选（KISS）的类似方法，用于鉴定对乳腺癌亚型具有特异性的p21活化激酶的新型致癌底物。预期这种高通量方法将加速鉴定新型药物靶标和生物标记物的过程。