Basic Research Driving Clinical Advances Against Cancer BASIC RESEARCH DISCOVERY CLINICAL BREAKTHROUGH CURRENT STATUS 1980s The human HER2 gene is identified and sequenced. 1998 FDA approves trastuzumab (Herceptin), an antibody targeting HER2, to treat patients with HER2-positive metastatic breast cancer. July 2023 So far, trastuzumab, alone, in combination with other drugs or as antibody-drug conjugates, has been approved by FDA to treat patients with certain types of breast, gastric, lung, and colorectal cancers. 1980s BCR-ABL protein, a product of the Philadelphia chromosome, is identified as a possible cause of chronic myelogenous leukemia (CML). 2001 FDA approves imatinib (Gleevec), a targeted therapeutic against BCR-ABL, for treatment of patients with CML. July 2023 So far, six therapeutics targeting BCRABL have been approved by FDA to treat CML. 1980s The human RET gene is identified and its rearrangements in thyroid cancer are documented. 2020 FDA approves selpercatinib (Retevmo), a molecularly targeted therapeutic that inhibits RET activity, to treat thyroid cancer. July 2023 So far, two RET-targeted therapies have been approved by FDA for treatment of lung and thyroid cancer, as well as any solid tumor based on a certain biomarker. 1980s The human PARP-1 gene is identified and its role in DNA repair is discovered. 1990s The human BRCA1 and BRCA2 genes are identified and their role in DNA repair is discovered. 2014 FDA approves olaparib (Lynparza), a molecularly targeted therapeutic that inhibits PARP activity, to treat women with advanced ovarian cancer who inherited mutations in BRCA1/2 genes. July 2023 So far, four PARP-targeted therapeutics have been approved by FDA for treatment of breast, ovarian, pancreatic, and prostate cancers. 1980s The human NTRK is identified as an oncogene and its rearrangements in colorectal and thyroid cancers are documented. 2018 FDA approves larotrectinib (Vitrakvi), a molecularly targeted therapeutic that inhibits NTRK activity, to treat children and adults whose tumors are carrying NTRK rearrangements. July 2023 So far, two NTRK-targeted therapies have been approved by FDA for treatment of any solid tumor based on NTRK rearrangements. SIDEBAR 6 AACR Cancer Progress Report 2023 Understanding the Path to Cancer Development 28
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