Decoding P21 Activated Kinase‐1 (PAK1) and Drug‐Resistance Enigma

Drug resistance, also known as chemoresistance, is a known impediment in fighting cancers. Pak1 (p21-activated kinase), a serine/threonine kinase, is a known oncogene implicated in tumor progression and associated with poor prognosis in cancer patients. Pak1 has been reported to be mechanistically contributing to drug resistance to tamoxifen and gemcitabine. Using an integrative approach, the present study investigated Pak1 and its precise role in conferring chemoresistance alongside other known kinases. Study identified 25 additional kinases contributing to resistance to 12 commonly used drugs in clinics for the treatment of breast, head and neck, and pancreatic cancers. The study analysis revealed that mutated Pak1 and more than one kinase were likely to be involved in drug resistance in patients associated with poor prognosis. The study concluded that the detection of altered kinases in resistant tumors is imperative, and a combination of kinase inhibitors could be useful for treatment rather than single agents to improve treatment outcomes.