Rina Plattner, PhD

The Plattner laboratory studies the process of cancer metastasis and therapeutic resistance. Most cancer deaths result from metastatic spread to distant organ sites. In no cancer type is this most striking than in melanoma. The cure rate for small, thin, non-metastatic melanomas is >98%; however, once melanomas have metastasized, the 5-year survival rate drops to 27% (2021 figures). Great strides have been made in detection and prevention; however, melanoma diagnoses still are on the rise, particularly in young adults. Treatment advances such as immunotherapy and targeted therapy (BRAF/MEK inhibitors) have revolutionized the treatment of metastatic melanoma. While the 5-year survival rate has only risen from 5% which it was 2010, this cure rate remains low. Some patients do not respond or can not tolerate immunotherapy, which can have durable responses in some patients. In contrast BRAF/MEK inhibitor therapy is only effective for patients with mutant BRAF melanoma (about 50%), and although the majority of these patients initially respond, nearly all eventually develop resistance to the regimen (1 year mean survival). Thus, there is an unmet need for additional therapies to prevent or reverse resistance and metastatic disease. The Plattner laboratory identified the ABL family of non-receptor tyrosine kinases (ABL1, ABL2) as novel drug targets in melanoma. These kinases are most known for their involvement in the development of human leukemia (such as chronic myelogenous leukemia-CML). Gleevec/imatinib, an inhibitor of the ABL family, was one of the first “smart” drugs developed, and imatinib and nilotinib (2nd generation inhibitors) have been standard of care therapies for CML for decades. Significantly, the Plattner laboratory was the first to demonstrate that, in addition to leukemia, ABL kinases also play a critical role in solid tumors, such as melanoma and breast cancer, indicating that drugs targeting these kinases may also be effective for treating these diseases. Seminal work from the laboratory showed that ABL kinases are highly activated in some breast cancers and melanomas, and their activation contributes to cancer proliferation, survival following nutrient deprivation, anchorage-independent growth, invasion, and metastasis. Previous studies in the laboratory focused on identifying novel pathways by which the ABL family drive breast cancer and melanoma invasion and metastasis using cancer cell lines (in vitro studies), animal models (in vivo studies) and patient samples. Currently, the laboratory is focusing on the role of ABL kinases during melanoma therapeutic resistance, and has identified a unique drug combination that reverses and prevents BRAF/MEK inhibitor resistance, in vivo. Her laboratory's exciting findings have led to a clinical trial to test this regimen in patients who have failed BRAF/MEK inhibitor therapy, and her current research is focused on dissecting the mechanisms by which ABL kinases drive resistance in different melanoma subtypes.