Evaluating candidate mediators of prostate cancer metastasis and neuro endocrine prostate cancer (NEPC) trans differentiation

评估前列腺癌转移和神经内分泌前列腺癌（NEPC）转分化的候选介质

• 批准号: 10241237
• 负责人: Meenalakshmi Chinnam
• 金额: $ 13.02万
• 依托单位: ROSWELL PARK CANCER INSTITUTE CORP
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-14 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10241237
• 关键词: Androgen Antagonists; Antiandrogen Therapy; Biochemistry; Cancer Relapse; Disease; Doctor of Philosophy; Endocrine; Epigenetic Process; Exhibits; Funding; Histology; Histopathology; Human; Journals; Laboratories; Malignant neoplasm of prostate; Mediator of activation protein; Molecular; Molecular Biology; Molecular Genetics; Mus; Mutation; Neoplasm Metastasis; Neurosecretory Systems; Nutritional Science; Pharmaceutical Preparations; Pharmacology; Postdoctoral Fellow; Publishing; RB1 gene; Research; Resistance; Science; Specimen; Testing; Validation; Variant; Wages; Work; androgen deprivation therapy; anticancer research; experience; improved; mouse model; novel; novel therapeutic intervention; programs; prostate cancer metastasis; prostate cancer model; resistance mechanism; response; therapy resistant; tumor; tumor progression

Prostate cancer relapsing from antiandrogen therapies can exhibit variant histology with altered lineage marker expression, suggesting lineage plasticity facilitates therapeutic resistance. Mechanisms underlying prostate cancer lineage plasticity are unknown. Our recent work published in Science uses mouse models of prostate cancer to demonstrate Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, metastasis, and antiandrogen resistance. The research program funded by R01 CA207757 proposes to identify molecular mechanisms underlying Rb1 and Trp53 function in this context and assess a novel therapeutic approach using epigenetic modulating drugs to improve responses to therapy. This R50 application proposes salary support for Meenalakshmi Chinnam, Ph.D. to support the R01 CA207757 research program. Dr. Chinnam works as a Research Associate in the laboratory of Dr. David Goodrich, unit director on this application. Dr. Chinnam has made significant contributions to Dr. Goodrich's research programs since 2004, and her work has been published in well-regarded journals. Dr. Chinnam is a skilled experimentalist with a broad background in pharmacology, molecular biology, molecular genetics, biochemistry and nutrition sciences. She has over 13 years of experience in cancer research. Relevant to this application, Dr. Chinnam has considerable experience using mouse models of prostate cancer and characterizing the histopathology of both mouse and human prostate cancer specimens. Dr. Chinnam will leverage this expertise to help generate and characterize novel mouse models proposed in R01 CA207757 to elucidate how Ezh2 or E2f1 activity influence lineage plasticity, cancer progression, and response to antiandrogens. She will also characterize human prostate cancer specimens for cross-species validation. Dr. Chinnam's contributions will be essential for successful completion of the R01 CA207757 research program.

抗雄激素治疗后复发的前列腺癌可表现为组织学变异