AFCR - CityU Innovation Series in Biomedicine

Abstract

The discovery of the association between epidermal growth factor receptor (EGFR) mutations and sensitivity to EGFR-tyrosine kinase inhibitors (TKIs) took place in 2004. Approximately 15% of patients with non-small cell lung cancer in the US and Europe and 30-50% of these patients in East Asia have this mutation. The discovery ushered in the era of precision medicine in lung cancer. The first chromosomal rearrangement that could be effectively targeted, ALK, was discovered 3 years later in 2007, present in approximately 5% of lung cancer patients. The therapeutic agents directed against these two targets have improved so now the EGFR-TKI, osimertinib, works for longer than a year and half and the expected survival is beyond 3 years. Osimertinib use has now expanded from EGFR mutant patients with advanced cancer to adjuvant therapy which reduces the chance or recurrence by 80% after surgical resection. Patients with ALK rearrangements treated with alectinib can be effectively treated for approximately 3 years and an expected survival of longer than 5 years. Eight more genomic changes have led to US FDA approvals for rarer events in lung cancer including ROS1 rearrangements, BRAF V600E mutations, NTRK rearrangements, RET rearrangements, MET exon 14 skip mutations, exon 20 EGFR mutations, HER2 mutations, and KRAS G12C mutations, each making up approximately 1-3% of lung cancer patients. The targeted agents for these oncogenic drivers have a response rate of 40-70% or more and a duration of response of approximately 9 months or longer. The list of genomic abnormalities that can be precisely treated with targeted agents now make up approximately 40% of NSCLC patients in the US and around the world.

Speaker Bio

Bruce E. Johnson, MD, is an Institute Physician at the Dana-Farber Cancer Institute, Professor of Medicine at Harvard Medical School and the Brigham and Women’s Hospital, and an ASCO Translational Research Professor. He is a Co-Leader of the Dana-Farber/Harvard Cancer Lung Cancer Program and Co-Director of the Center for Cancer Genomics at the Dana-Farber Cancer Institute. He received his undergraduate degree from Harvard University and his medical degree from the University of Minnesota, and he trained in internal medicine at the University of Chicago. Dr Johnson completed his medical oncology training at the National Cancer Institute, where he served as a faculty member from 1985 to 1998 and as head of their Lung Cancer Biology section for 6 years. He came to Dana-Farber in 1998 to head the Lowe Center for Thoracic Oncology and served in that position from 1998 to 2013. He transitioned to be the Chief Clinical Research Officer at the Dana-Farber Cancer Institute from 2013 to 2021 and is now a Senior Advisor to the President and CEO of the Dana-Farber Cancer Institute.

Dr Johnson was one of the investigators who discovered the link between mutations of the epidermal growth factor receptor (EGFR) and sensitivity to EGFR- tyrosine kinase inhibitors and is one of the patent holders for EGFR mutation testing. He has published more than 290 research articles on a variety of topics, including the molecular basis of lung cancers and the development of targeted therapies for patients with specific genomic alterations in lung cancer.