PPM1D, a Promising Therapeutic Target Uncovered Through shRNA Library Screening, Plays a Pivotal Role in Regulating the Progression of Breast Cancer

Breast cancer a leading global cause of mortality is witnessing a rapid increase in incidence, especially in India. The focus on understanding the molecular basis of carcinogenesis for effective cancer defense is growing rapidly. Targeting specific molecular aspects of cancer development has been identified as a more precise treatment approach. Enhancing comprehension of the factors triggering cancer initiation, progression, and evolution is crucial. Challenges in cancer therapeutics arise from issues like delayed detection, non-specific systemic distribution, multi-drug resistance, and inadequate drug concentration delivery to the tumor site. Numerous reports highlight the effective use of RNA interference (RNAi) to attenuate cancer growth using both in vitro and in vivo models. PPM1D, an oncogene amplified and overexpressed in various tumors, including breast, serves as a negative regulator of the p38MAP kinase-p53 signaling pathway and is implicated in other crucial cell survival pathways. Continuous research on PPM1D and its association with cancer is essential, contributing significantly to the understanding and treatment of cancer. PPM1D phosphatase plays a pivotal role as a repressor of the p53 pathway and response to the DNA damage. Overexpression of PPM1D compromises p53 function, enhancing tumor growth, often in association with the activation of other oncogenes. The amplification, overexpression, or mutation of PPM1D is closely linked to various human tumors. Silencing PPM1D in cancer cells results in decreased cell proliferation and migration. Our results revealed that PPM1D knocked-down tumor xenograft models showed drastic reduction of breast tumor growth suggesting that PPM1D acts as important therapeutic target for the management of breast cancer.