DYNAMIC MOLECULAR EVOLUTION OF TREATMENT RESISTANT CANCER

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Project Summary/Abstract: Cancer is the second leading cause of death in the United States. In some patients, cancer can be cured with surgery and/or radiation. Many patients will develop advanced disease that must be managed with various systemic medications and treatments. Unfortunately, the majority of patients in this group will eventually develop treatment resistant cancer, which is often lethal. Despite its importance, our understanding of how this resistance develops and evolves is limited. The primary challenge is that the study of treatment resistance requires obtaining tumor samples before, during, and after it develops. However, obtaining these samples involves surgical or other invasive procedures that carry some risk of causing a complication which could harm the patient. Repeatedly obtaining tissue samples for research is not feasible for the majority of patients. We propose to use a new “liquid” biopsy technique in which molecular information about the tumor is collected from serial blood samples, which patients with cancer are frequently providing for a variety of laboratory tests already. This information can then be used to understand how treatment resistance develops and how it evolves over time. This will allow us to identify potential strategies to overcome this resistance, as well as create tests to pick it up early so that treatment can be adjusted before the cancer grows and the patient gets sicker. This strategy could be used across cancers and treatments and change the paradigm in how we understand cancer progression as well as change how we monitor and treat patients.