Federica Di Nicolantonio, Ph.D.
Changes in DNA methylation in response to environmental stimuli may be associated with an increase in the risk of neoplastic transformation. Changes in epigenetic regulatory events are also key to maintaining the tumorigenic phenotype. The laboratory of Cancer Epigenetics investigates epigenetic biomarkers for personalized cancer detection and therapy.
- Methylation changes are considered an early event in colorectal carcinogenesis. For this reason, DNA methylation markers have been proposed for early CRC detection using stool or blood samples. We have recently identified a panel of loci that are differentially hypermethylated in colorectal cancer patient plasma samples compared to self-declared healthy individuals (Barault L et al., Gut. 2018 Nov;67(11):1995-2005. pii: gutjnl-2016-313372).
- In order to deliver precision oncology for advanced colorectal cancer patients, we have validated MGMT hypermethylation in solid and liquid biopsies as a predictive marker of response to alkylating agent based therapy (Barault L et al., Ann Oncol. 2015; 26:1994-9); Amatu A, Barault L et al., Ann Oncol. 2016;27:1062-7).
- Identifying the molecular bases of response or resistance to first-line anti-cancer treatments may aid in designing and testing sequences of drugs rationally designed on the modifications induced by the first agent on the tumor molecular landscape. In this regard, we have unveiled the role of receptor tyrosine kinase signaling or MAPK pathyway molecular alterations as biomarkers of acquired resistance to BRAF combination therapies in BRAF mutant colorectal patients and have shown how this knowledge can help designing further salvage treatment lines (Oddo D et al., Cancer Res. 2016;7 6:4504-15; Pietrantonio F et al., Cancer Discov. 2016; 6:963-71; Oddo D et al., Br J Cancer. 2017;117:347-352).
Current and future research interests include:
- assessing methylation in liquid biopsy as a marker of minimal residual disease in patients who have undergone primary colonic tumor resection;
- assessing molecular markers of response/relapse to temozolomide-based chemotherapy in advanced colorectal cancer patients, including the impact of temozolomide on the tumor molecular landscape;
- redefining the epigenetic landscape of BRAF mutant colorectal cancer for prognostic and predictive stratification;
- investigating the impact of metabolic and tumor microenvironment changes on enzymes involved in DNA methylation and their role in modulating anticancer drug response.