Nizar Batada: Genomic and computational cancer biology
The immune system protects the human body not only against foreign pathogens, but also against tumor cells.
Precision Cancer Therapy
Oncologists want to know what therapies to give to their patients. The concept of precision medicine, which is also known as targeted therapy, in cancer care focuses on identifying actionable molecular abnormalities present within an individual tumor. However, use of targeted therapies requires biomarkers to identify patients that will benefit from available treatment options. Our long-term goal is to develop an algorithm based on the empirical mutational spectra to identify patients whose tumors are defective in DNA repair and suggest candidate drugs that would be beneficial.
Evasion Of Anti-Tumor Immunity
a. Identifying epigenetic aberrations in tumor that contribute to evasion of immune surveillance
The immune system protects the human body not only against foreign pathogens, but also against tumor cells. Expression of cell-surface molecules with tumor-specific mutations (known as neoantigens) plays a crucial role in the efficient recognition and elimination of cancer cells by the immune system. Clinical findings have confirmed that immunotherapy has a real transformative potential for treating a wide variety of cancers. Unfortunately, as yet only a small proportion of patients benefit from immunotherapy. Recognizing the specific adaptive resistance mechanisms in each tumor will allow the development of immunotherapies tailored to block how a particular cancer protects itself from the immune system. We will integrate exome-seq, DNA methylation and RNA-seq data from the same tumor published by TCGA in order to identify epigenetic aberrations that suppress immune response. Our work will contribute to the identification of epigenetic drugs that would lead to stronger immune response when used in combination with existing immuno-modulatory drugs.
b. Identification of patient subsets most likely to benefit from immunotherapy
The advantage of immune-based therapies is that it works on a diverse range of tumor types, that is less likely to lead to resistance and that it has relatively low side effects since tumors would be attacking tumor-specific antigens that are absent in normal cells. However, immunotherapies are expensive and thus there is a need for determining which subgroups of patients are likely to respond to various types of immunotherapy. In collaboration with oncologists, we will extend our work by identifying local or circulating biomarkers that predict response to immunomodulatory drugs or therapies. Our work will help to identify patients that are likely to benefit from immunotherapy and also help identify ways in which immunotherapy resistant tumors can be made more immunogenic.