1). Drivers of disease progression in bladder cancer
2). HER2 and FGFR3 as therapeutic targets
3). Chromatin modifying gene mutations in bladder cancer
4). Resistance to BRAF-MEK inhibitors
The Solit laboratory performs integrated analyses of tumor and normal tissues and patient-derived and engineered models to identify novel drug targets and mechanisms of cancer drug resistance.
Our research is based on the underlying hypothesis that the ability to inhibit an oncogenic pathway and block cancer growth will vary based on cell lineage and the complement of mutations within the tumor. To develop rational therapies for cancer patients, we must define not only the spectrum of genetic changes within individual tumors but also the mechanisms by which these alterations support tumor growth, survival, metastasis, and other hallmarks of cancer. While much of our current work is focused on bladder cancer, our studies take a pan-cancer approach to allow for the identification of lineage-specific factors that influence drug response.
Biography
David Solit, MD is a graduate of the University of Pennsylvania School of Medicine, a practicing Medical Oncologist and a Laboratory Scientist. Dr. Solit pioneered the use of whole genome sequencing methods to identify occult predictors of drug response, work that served as the basis for the NCI Extraordinary Responder Initiative. As the inaugural Director of the Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Dr. Solit leads a multidisciplinary team of clinicians, geneticists, bioinformaticians and laboratory scientists whose mission is to integrate molecular and clinical information to develop therapies that are individualized to each patient’s cancer.
Distinctions:
Inducted, Association of American Physicians (2019)
Inducted, American Society of Clinical Investigation (2011)
Boyer Award for Excellence in Clinical Research (2007)
Doris Duke Translational Research Award (2001)
Selected Publications:
Poulikakos P, Persaud Y, Janakiraman M, Kong X, Ng C, Moriceau G, Shi H, Atefi M, Bjoern Titz B, Gabay MT, Salton M, Dahlman K, Tadi M, Wargo J, Flaherty K, Kelley M, Misteli T, Chapman P, Sosman J, Graeber T, Ribas A, Lo R, Rosen N, Solit D. RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E). Nature, 480(7377):387-90, 2011 Nov 23 [Epub ahead of print]. PMID: 22113612. PMCID: PMC3266695.
Iyer G, Hanrahan A, Milowsky M, Al-Ahmadie H, Scott S, Janakiraman M, Pirun M, Sander C, Socci N, Ostrovnaya I, Viale A, Heguy A, Peng L, Chan T, Bochner B, Bajorin D, Berger M, Taylor B, Solit D. Genome sequencing identifies a basis for everolimus sensitivity. Science, 2012 338(6104):221. Aug 23. [Epub ahead of print]. PMID: 22923433.
Hyman DM, Piha-Paul SA, Won H, Rodon J, Saura C, Shapiro GI, Juric D, Quinn DI, Moreno V, Doger B, Mayer IA, Boni V, Calvo E, Loi S, Lockhart AC, Erinjeri JP, Scaltriti M, Ulaner GA, Patel J, Tang J, Beer H, Selcuklu SD, Hanrahan AJ, Bouvier N, Melcer M, Murali R, Schram AM, Smyth LM, Jhaveri K, Li BT, Drilon A, Harding JJ, Iyer G, Taylor BS, Berger MF, Cutler RE Jr, Xu F, Butturini A, Eli LD, Mann G, Farrell C, Lalani AS, Bryce RP, Arteaga CL, Meric-Bernstam F, Baselga J, Solit DB. HER kinase inhibition in patients with HER2- and HER3-mutant cancers. Nature. 2018 Feb 8. Epub 2018 Jan 31. PMID: 29420467. PMCID: PMC5808581.
Jonsson P, Bandlamudi C, Cheng ML, Srinivasan P, Chavan SS, Friedman ND, Rosen EY, Richards AL, Bouvier N, Selcuklu SD, Bielski CM, Abida W, Mandelker D, Birsoy O, Zhang L, Zehir A, Donoghue MTA, Baselga J, Offit K, Scher HI, O'Reilly EM, Stadler ZK, Schultz N, Socci ND, Viale A, Ladanyi M, Robson ME, Hyman DM, Berger MF*, Solit DB*, Taylor BS*. Tumour lineage shapes BRCA-mediated phenotypes. Nature. 2019 571(7766):576-579, doi: 10.1038/s41586-019-1382-1. Epub 2019 Jul 10, PMCID: PMC7048239. *Co-corresponding
Chakravarty D, Solit DB. Clinical cancer genomic profiling. Nature Reviews Genetics. 2021, Aug;22(8):483-501. doi: 10.1038/s41576-021-00338-8., 2021 Mar 24. doi: 10.1038/s41576-021-00338-8. Epub 2021 Mar 24. PMID: 33762738.
