Phosphatase magnesium-dependent 1 δ (PPM1D), serine/threonine protein phosphatase and novel pharmacological target in cancer

Abstract Aberrations in DNA damage response genes are recognized mediators of tumorigenesis and resistance to chemo- and radiotherapy. While protein phosphatase magnesium-dependent 1 δ (PPM1D), located on the long arm of chromosome 17 at 17q22-23, is a key regulator of cellular responses to DNA damage, amplification, overexpression, or mutation of this gene is important in a wide range of pathologic processes. In this review, we describe the physiologic function of PPM1D, as well as its role in diverse processes, including fertility, development, stemness, immunity, tumorigenesis, and treatment responsiveness. We highlight both the advances and limitations of current approaches to targeting malignant processes mediated by pathogenic alterations in PPM1D with the goal of providing rationale for continued research and development of clinically viable treatment approaches for PPM1D-associated diseases.