Alice T. Shaw

Alice T. Shaw, MD, PhD, is the Director of Thoracic Oncology at Massachusetts General Hospital (MGH) and a Professor of Medicine at Harvard Medical School, recognized globally for her pioneering work on ALK- and ROS1-driven non-small cell lung cancer. She was among the first investigators to demonstrate the clinical activity of crizotinib in ALK-positive NSCLC patients and to characterize mechanisms of resistance to ALK inhibitors, foundational work that has shaped the entire generation of next-line ALK-directed therapies. Her laboratory integrates molecular profiling, circulating tumor DNA analysis, and mouse model experiments to understand the biology of ALK- and ROS1-rearranged cancers and to devise strategies for overcoming resistance. Shaw's contributions to the development of lorlatinib, a third-generation ALK/ROS1 inhibitor, were central to its approval in patients with ALK-positive NSCLC following progression on prior ALK inhibitors, including those with active brain metastases. She identified compound ALK mutations as a mechanism of resistance to second-generation ALK inhibitors and demonstrated that lorlatinib retains activity against these compound mutations, directly informing patient selection and rational sequencing of ALK inhibitors. Her work on ROS1-rearranged NSCLC has similarly defined the natural history of resistance to ROS1-directed therapy and evaluated novel agents including entrectinib and lorlatinib. Beyond her scientific contributions, Shaw is a dedicated mentor and educator who has trained numerous fellows and junior faculty. She is a sought-after speaker at international meetings and has contributed extensively to guideline development through ASCO, NCCN, and IASLC. Her research program at MGH continues to pioneer the understanding of acquired resistance and to develop novel therapeutic strategies for molecular subgroups of lung cancer.