Layman’s Explanation

Natural selection is the basis of evolution: whoever can withstand changing conditions can reproduce, and those offspring ultimately dominate a population. This is ubiquitously observed in nature: from mice changing their fur color to blend in with their surroundings, to bacteria developing antibiotic-resistant mechanisms. Cancer cells are no exception. Modern targeted therapies are aimed at killing cancer cells that have specific cancer-like traits, such as certain receptors, to avoid killing “good cells”. However, cancer cells are often smart enough to modify their targeted receptors to hide from these therapeutics. These cancer cells can continue to replicate, and ultimately cause a patient to be unresponsive to therapeutics.

Our lab studies the evolution of cancer resistance in the context of Acute Myeloid Leukemia (AML), which is a type of devastating blood cancer. There is a receptor called Fms-Like Tyrosine Kinase-3 (FLT3) that is commonly mutated in AML, which is associated with a particularly poor prognosis, in large part due to resistance to first line therapies. We study the FLT3 receptor and its associated cellular pathways to determine how they operate when cells become resistant to anti-cancer drugs. We hope that by studying how cells evade our current therapeutic modalities, we can create better treatment options and ultimately cure AML.

Scientific Explanation 

Despite being implicated in almost a third of AML cases, the Fms-Like Tyrosine Kinase-3 (FLT3) receptor remains an enigma to the scientific community. Typically, patients have an activating FLT3 internal tandem duplication (ITD) that causes over-expression of a myriad of downstream signals. Patients with FLT3 ITD mutations typically have poor prognoses, and mutations both upstream and downstream of the FLT3 pathway are often implicated in therapeutic resistance.

We employ a “bedside to bench and back” approach to the problem of cancer drug resistance, founded on the belief that the ultimate pathway to improved cancer therapy begins with translational studies that utilize samples from patients who have undergone therapy in real time. This strategy allows us to interrogate how tumors can evolve under the selective pressure of cancer therapy and allows us to devise ways to circumvent these evolutionary adaptations. We ultimately aim to develop novel therapeutics while uncovering facts about the basic science behind AML therapeutic resistance.