Molecular Cancer Medicine
PI Kazi Julhash Uddin
Despite incredible progress in the treatment of cancer, the cure rate remains low due to the fact that almost all cancer patients develop resistance to anticancer therapies. This results in as many as 90% of cancer-related deaths in various types of cancer. Consequently, identification of the factors that drive the development of therapy resistance is a pressing issue in the field. Cancer treatment induces specific genetic and epigenetic changes in cancer cells and in the microenvironment in which cancer cells reside, contributing to resistance. Mechanistically, resistance is highly specific to each cancer subtype and therapy, and most likely involves multiple molecular interactors. An understanding of the molecular mechanisms of resistance to anti-cancer therapy will facilitate the development of novel therapeutic regimens.
Receptor tyrosine kinases (RTKs) have long been known to be involved in cancer progression and have been used as therapeutic targets. RTKs are cell surface receptors with special structural and biological characteristics that respond to environmental cues by initiating appropriate signaling cascades. Several RTKs are mutated or overexpressed in cancer, and many of them cooperate to mediate therapy resistance. Our research focuses on deciphering the molecular mechanisms of resistance to anti-cancer therapy in leukemia and ovarian cancer by targeting the RTK signaling axis. We use state-of-the-art technology, including live imaging of small animals, high-resolution microscopy, RNA sequencing, and mass spectrometry, and disease-relevant models, including patient-derived xenografts, in vivo bone marrow transplantation models, and patient material.
Deciphering the role of RTKs in anticancer therapy resistance will improve the general understanding of basic biology of receptor regulation and, in the long term, inform the development of more effective therapeutic regimens.