Defining Over-expression of MYBL2 as a Driver of Lethal Prostate Cancer
Abstract
Prostate cancer (PCa) is the second most frequently diagnosed cancer type among men in America. Currently, the cumulative five-year survival rate for patients with prostate cancer is over 98 percent. Unfortunately, the average survival for men with metastatic or recurrent prostate cancer drops considerably. Second-generation androgen deprivation therapies (ADT) have provided significant life-extending therapies for recurrent, or metastatic castration resistant prostate cancer (mCRPC) patients. A particular resistant, aggressive subset of these mCRPC tumors is independent of AR activity (CRPC-AI). CRPC-AI primarily adapt to ADT via lineage plasticity rather than a result of resistant mutations, adopting a phenotype no longer reliant on AR expression and signaling. These tumors may display neuroendocrine features, a stem or basal cell-like phenotype, altered kinase signaling, and characteristic epigenetic alterations, including upregulation of EZH2. Currently there is no therapeutic option to provide long term durable response to CRPC-AI patients. Therefore, a deeper knowledge of molecular mechanisms driving CRPC-AI will significantly move the field forward to provide discoveries for therapeutic vulnerabilities to successfully inhibit progression or treat CRPC-AI. From this, we have a novel candidate, MYBL2, that may act as a master-regulator transcription factor that upon RB1 LOF drives linage plasticity and resistance to ADT.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2021
- Accession Number
- AD1145081
Entities
People
- Christopher Sweeney
- Leigh Ellis
Organizations
- Cedars-Sinai Medical Center