Precision Molecular Pathology of Prostate Cancer

Brian D. Robinson, MD Weill Cornell MedicineNew York, NYUSA

Part I. General principles.- Approach to patient.- Etiology.- Precursor and pre-invasive lesions of prostate cancer.- Prostatic adenocarcinoma: morphologic spectrum, Gleason scoring, etc.- Genetic susceptibility.- DNA damage repair, BRCA mutations, DNA adducts, SNPs.- Racial differences.- Cancer stem cells Part II. Molecular signatures of primary prostate cancer.- SNPs.- Copy number variation/chromosomal aberration (PTEN deletion, etc.).- Gene fusions (TMPRSS2:ERG, etc.).- Gene expression arrays.- Next generation sequencing (point mutations, indels, etc.).- Epigenetic changes (chromatin remodeling, etc.).- Proteomics.- Metabolomics.- miRNA and lncRNA Part III. Molecular signatures of advanced prostate cancer.- Lymph node metastasis.- Bone metastasis a.- RANKL, Src kinases, endothelins, bisphosphonates.- Visceral metastasis a.- Role of extracellular matrix, angiogenesis, epithelial-mesenchymal transition (EMT), inflammation.- Castration resistant prostate cancer (CRPC).- Neuroendocrineprostate cancer (NEPC) Part IV. Key molecular pathways in prostate cancer development and progression.- Androgen receptor in carcinogenesis.- Androgen receptor in progression (CRPC).- PI3K/Akt/mTOR/PTEN and ERK/MAPK pathways.- Cell cycle regulators (p53, etc.).- DNA damage repair.- Tyrosine kinase signaling (EGFR, VEGFR, PDGFR, FGFR, IGFR, etc.).- Cytoskeletal function (microtubules and taxane therapy) Part V. Precision medicine approach: Diagnosis, treatment, prognosis.- Molecular diagnosis.- Molecular imaging.- Molecular prognostic markers/tests.- Molecular targeted therapies.- Towards molecular classification of prostate cancer.