children and adults who live longer and fuller lives after a cancer diagnosis. As of January 1, 2022, the most recent date for which such estimate is available, more than 18 million individuals with a history of cancer were alive in the United States (7). Recent studies indicate that the number of U.S. individuals living despite being diagnosed with metastatic disease has increased since the 1990s and this number is estimated to grow considerably in the coming years (8). This increase is attributable to the advances in treatments that are available for patients with metastatic cancers. Cancer: An Ongoing Public Health Challenge Although incredible progress has been made against cancer, it continues to be an enormous public health challenge in the United States and around the world (see Sidebar 4, p. 22). In the United States alone, an estimated 1,958,310 new cases of cancer will be diagnosed in 2023 and 609,820 people will Research Driving Progress Against Lung Cancer Discoveries over the past three decades have identified numerous cellular pathways that drive lung cancer development. Among these are alterations, also referred to as mutations (see Sidebar 7, p. 30), in genes such as Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), epidermal growth factor receptor (EGFR), fibroblast growth factor receptor (FGFR), anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1), rearranged during transfection (RET), mesenchymal-epithelial transition factor (MET), neurotrophic tropomyosin receptor kinase (NTRK), and human epidermal growth factor receptor 2 (HER2). Research has also shown that cancer cells evade destruction by the immune system because they have high levels of proteins that can attach to and trigger brakes on immune cells, stopping them from attacking cancer cells. Collectively, these discoveries have laid the foundation for the development of molecularly targeted therapeutic and immunotherapeutic agents, many of which have yielded remarkably lasting responses for patients with lung cancer. Indicated on the timeline are the first FDA approvals for lung cancer of molecularly targeted therapeutics, novel diagnostic agents, and immunotherapeutics with a unique mechanism of action. Thanks to these clinical breakthroughs along with steep reduction in U.S. smoking rate, lung cancer mortality is declining rapidly. In fact, the decrease in lung cancer mortality per year accelerated from 0.9 percent between 1995 and 2005 to 2.4 percent between 2005 and 2014 to nearly five percent between 2014 and 2020 (2,4). FIGURE 1 FIRST FDA APPROVALS OF THERAPEUTICS WITH UNIQUE MECHANISMS OF ACTION 2010 2000 2005 2015 1970 2020 1978 Single agent therapy (cisplatin) 2003 EGFR inhibitor (gefitinib) 2011 ALK/ROS-1 inhibitor (crizotinib) 2006 Angiogenesis inhibitor (bevacizumab) 2018 Targeted therapy based on tumor-agnostic biomarker (larotrectinib for NTRK gene fusions) 2015 Mutant EGFRT790M inhibitor (osimertinib) Immune checkpoint inhibitor (pembrolizumab) 2017 Immunotherapy based on tumor-agnostic biomarker (pembrolizumab for MSIh-dMMR status) MEK/RAF inhibitor (dabrafenib & trametinib) 2021 Bispecific antibody (amivantamab-vmjw) KRAS G12C inhibitor (sotorasib) 2016 cobas EGFR Mutation test (cobas liquid biopsy CDx) 2020 Immune checkpoint inhibitors (nivolumab & ipilimumab) Liquid biopsy NGS test (Guardant360 CDx) RET inhibitor (selpercatinib) MET inhibitor (capmatinib) 2022 HER-2 inhibitor (fam-trastuzumab deruxtecan-nxki) Companion Diagnostic Chemotherapy Molecularly Targeted Therapy Immunotherapy AACR Cancer Progress Report 2023 Cancer in 2023 14
RkJQdWJsaXNoZXIy NTkzMzk=