Research topics
Personalized Cancer Medicine

Background
Personalized cancer medicine based on the genetic milieu of individual tumors has long been postulated but until recently this concept was not supported by clinical evidences. In the past five years it has been demonstrated that cancers can be diagnosed and classified on the basis of their molecular profile. Furthermore, the pattern of genetic alterations present in individual tumours can now be used to predict their clinical outcome. Finally, the success of drugs aimed at inhibiting mutated genes has shown that cancer-specific genetic alterations are legitimate targets for therapy.

Achievements
Over the last five years, we have pioneered a research program that has translated into the first example of personalized treatment of colorectal cancer (CRC).  Current treatment of this disease include EGFR-targeted therapy with monoclonal antibodies (moAbs), but these agents provide significant clinical benefit in only about 10% of unselected patients. Using clinical samples and innovative cellular models we have shown that CRC harboring molecular alterations in downstream effectors of the EGFR (KRAS, BRAF, PIK3CA) are resistant to treatment with the EGFR-targeted moAbs. These findings were confirmed by independent laboratories with such compelling evidence that they were rapidly translated into clinically applicable predictive biomarkers (genomic signatures) currently used to select patients for anti EGFR therapy.

Goals
Our future goals include the development of new personalized cancer treatments by investigating the association between molecular characteristics of individual tumors and response/resistance to targeted anticancer therapeutics in colorectal as well as other malignancies. Our long term goal is to provide patient and tumor -specific “frames” of molecular determinants that can be used to drive the decision process for tailored cancer treatment.

Internal collaborations
Lab of Vascular Oncology: The role of oncogenic mutations in the interplay between cancer cells and the tumor vasculature; Lab of Molecular Pharmacology: The molecular basis of resistance to anti EGFR targeted therapies in colorectal cancer; Laboratory of Oncogenomics: Transcriptional signatures of cancer mutations