Melica N. Brodeur, MD, MSc

The types of research carried out touch upon the following main themes:

• Epigenetic modulation and impact on the tumor microenvironment: The tumor microenvironment (TME) have become an important area of research. We now understand that there are immunosuppressive factors that promote tumorigenesis and tumor-immune cell interactions and immune phenotypic changes that influence response/resistance to treatment.
• Development and validation of predictive/prognostic biomarkers: Part of our mission is to personalize patients’ treatment and to provide the right treatment, at the time to the right patient. Identifying biomarkers to predict response to a given treatment can potentially avoid undertreating or overtreating patients. Using a surrogate marker for DNA repair pathways deficiencies are currently a promising avenue for gynecologic cancers. Furthermore, non-invasive tests, such as circulating tumor DNA, is a new field of interest in our laboratory.
• Development of a preclinical model platform: This theme addresses two important areas: 1) to understand the basic biology and etiology of gynecologic cancer initiation and progression, and 2) to establish clinically relevant preclinical models to a) improve precision medicine and b) to develop a platform for for accurate prediction of therapeutic efficacy of targeted therapies in clinical trials
• Targeting DNA repair pathways in gynecological cancers: Alteration in the expression of repair genes is a common feature of many gynecological cancers. DNA repair alterations can lead to tumor initiation and may be due to genetic mutations, transcriptional regulation, and epigenetic modifications. These alterations may also present vulnerabilities to these cancer cells that can be exploited. Thanks to the support of our patient-partners, our team studies donated patient biospecimens to determine changes in DNA repair proteins in the development of ovarian and endometrial cancer.
• Understanding response to immunotherapy combinations in recurrent MMRp endometrial cancers: Molecular and tumor microenvironment profiling of these cancers will help our team understand why some patients respond well to combination Pembrolizumab and Lenvatinib. Given the significant toxicities associated with this drug combination, our team is also investigating how to predict adverse events in these patients to mitigate them earlier.
• Understanding response to immunotherapy in recurrent ovarian clear cell cancers: Molecular and tumor microenvironment profiling of these cancers will help our team understand why some patients respond well to combination Pembrolizumab. Given the significant toxicities associated with this drug , our team is also investigating how to predict adverse events in these patients to mitigate them earlier.
• Characterizing subtypes of vulvar cancer: Our goal is to molecularly profile HPV-independent vulvar cancers and compare them to HPV-dependent vulvar cancers. Correlation with clinical outcomes will enable us to better understand cancer drivers and identify new therapeutic targets.