Small molecules, big impact: 20 years of targeted therapy in oncology Review
| Authors: | Bedard, P. L.; Hyman, D. M.; Davids, M. S.; Siu, L. L. |
| Review Title: | Small molecules, big impact: 20 years of targeted therapy in oncology |
| Abstract: | The identification of molecular targets and the growing knowledge of their cellular functions have led to the development of small molecule inhibitors as a major therapeutic class for cancer treatment. Both multitargeted and highly selective kinase inhibitors are used for the treatment of advanced treatment-resistant cancers, and many have also achieved regulatory approval for early clinical settings as adjuvant therapies or as first-line options for recurrent or metastatic disease. Lessons learned from the development of these agents can accelerate the development of next-generation inhibitors to optimise the therapeutic index, overcome drug resistance, and establish combination therapies. The future of small molecule inhibitors is promising as there is the potential to investigate novel difficult-to-drug targets, to apply predictive non-clinical models to select promising drug candidates for human evaluation, and to use dynamic clinical trial interventions with liquid biopsies to deliver precision medicine. © 2020 Elsevier Ltd |
| Keywords: | cancer survival; gene mutation; overall survival; review; erlotinib; drug efficacy; nonhuman; drug approval; imatinib; unindexed drug; gene amplification; dasatinib; oncogene; gene rearrangement; gefitinib; nilotinib; neratinib; personalized medicine; drug indication; molecularly targeted therapy; midostaurin; bosutinib; crizotinib; vemurafenib; dabrafenib; afatinib; dacomitinib; ibrutinib; ponatinib; human; priority journal; palbociclib; ceritinib; alectinib; abemaciclib; ribociclib; venetoclax; encorafenib; brigatinib; osimertinib; gilteritinib; lorlatinib; malignant neoplasm; pexidartinib; acalabrutinib; zanubrutinib; amg 510; jnj 74699157; mrtx 849 |
| Journal Title: | Lancet |
| Volume: | 395 |
| Issue: | 10229 |
| ISSN: | 0140-6736 |
| Publisher: | Elsevier Science, Inc. |
| Date Published: | 2020-03-28 |
| Start Page: | 1078 |
| End Page: | 1088 |
| Language: | English |
| DOI: | 10.1016/s0140-6736(20)30164-1 |
| PUBMED: | 32222192 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Review -- Export Date: 1 May 2020 -- Source: Scopus |
