Current trends and opportunities in targeting p21 activated kinase-1(PAK1) for therapeutic management of breast cancers.

• Breast cancer is a multifaceted disease, which is mainly caused due to deregulations in multiple signalling cascades. • A proteogenomic study on breast (normal/cancer) tissues showed that PAK1 is an outlier kinase which is frequently overexpressed in cancer tissues. • P21 activated kinase (PAK1) is an oncogene which is involved in breast cancer progression by phosphorylation of it's substrates and it is also involved in tamoxifen resistance. • Kinase Interacting Substrate Screening (KISS) methodology can be used to screen subtype specific substrates of PAK1 for identification of druggable targets and biomarkers. 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. [ABSTRACT FROM AUTHOR]