Precision Oncology

Deep molecular profiling of cancer genomics has identified molecular subtypes with distinct clinical trajectories and responses to therapeutics. We have used a unique rapid autopsy program and collaborative efforts supported by a StandUpToCancer Dream Team award, to identify the spectrum of genomic and gene expression alterations that occur in advanced prostate cancer. These studies have identified subcategories of prostate cancer partitioned by tumor suppressor loss (TP53/RB1), mismatch DNA repair deficiency (MSH2/6), homology-directed repair deficiency (BRCA1/2), tandem duplications (CDK12), as well as phenotypes that include amphicrine tumors.

Questions and Projects

  • Are particular subclasses of prostate cancers susceptible to specific therapeutics: e.g. mismatch repair and immune checkpoint blockade; homology-directed repair deficiency and PARPi?
  • Do particular subtypes influence responses to AR-directed therapy?
  • Do particular genomic aberrations promote cell plasticity? Transdifferentiation?'
  • Can subtypes be ascertained using minimally-invasive methods such as circulating tumor cells or circulating tumor DNA?
  • How do mutations in epigenetic control genes influence cancer development?
  • What are the influences of specific genomic aberrations and interactions with the tumor microenvironment?
  • How substantial is intratumor heterogeneity? Does it influence treatment responses?
graphic showing diversity index of tumor molecular heterogeneity within and between individuals.
Diversity index of tumor molecular heterogeneity within and between individuals.


  • Kumar A. Exome sequencing identifies a spectrum of mutation frequencies in advanced and lethal prostate cancers. Proc Natl Acad Sci U S A. 2011 Oct 11;108(41):17087-92.
    PMID: 21949389
  • Robinson D, et al. Integrative clinical genomics of advanced prostate cancer. Cell. 2015 May 21;161(5):1215-28. PMID: 26000489
  • Pritchard CC. Complex MSH2 and MSH6 mutations in hyper-mutated microsatellite unstable advanced prostate cancer. Nat Comm. 2014 Sep 25;5:4988. PMID: 21949389
  • Kumar A. Substantial Interindividual and Limited Intra-individual Genomic Diversity Among Tumors from Men with Metastatic Prostate Cancer. Nat Medicine. 2016 Apr;22(4):369-78. PMID: 26928463