Therapeutic developments in pancreatic cancer Journal Article
| Authors: | Hu, Z. I.; O'Reilly, E. M. |
| Article Title: | Therapeutic developments in pancreatic cancer |
| Abstract: | Pancreatic ductal adenocarcinoma (PDAC) has a rising incidence and is one of the most lethal human malignancies. Much is known regarding the biology and pathophysiology of PDAC, but translating this knowledge to the clinic to improve patient outcomes has been challenging. In this Review, we discuss advances and practice-changing trials for PDAC. We briefly review therapeutic failures as well as ongoing research to refine the standard of care, including novel biomarkers and clinical trial designs. In addition, we highlight contemporary areas of research, including poly(ADP-ribose) polymerase inhibitors, KRAS-targeted therapies and immunotherapies. Finally, we discuss the future of pancreatic cancer research and areas for improvement in the next decade. The incidence of pancreatic ductal adenocarcinoma (PDAC) is rising. In this Review, Hu and O'Reilly summarize the latest advances and clinical trials for the treatment of PDAC, including biomarkers, targeted therapies and immunotherapy as well as novel clinical trial designs. They also discuss emerging therapeutic options for this disease. Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy, with cytotoxic chemotherapy remaining the mainstay of treatment for most patients.Ongoing trials are evaluating 'classical' versus 'basal-like' expression signatures to inform the therapeutic selection of standard cytotoxic regimens.Small subsets of patients, including those with mutations in , , and SG12C, rare fusions (, ), and mismatch repair deficiency, benefit from targeted therapies.KRAS is a critical target for therapeutic evaluation in PDAC and proof-of-principle approaches have validated targeting in G12C; ongoing trials are evaluating allele-specific inhibitors and pan-(K)RAS inhibitors against the more common allele variants G12D, G12V and G12R.Immune-checkpoint inhibitor blockade and other immune therapies have not had utility for most patients with PDAC; however, select rare individuals beyond mismatch repair deficiency have seen major benefit, leading to optimism that these results can be expanded to a broader patient population.Clinical trial design strategies are changing and PDAC is a prototypic disease to investigate novel drug development paradigms; innovation in clinical trial design has led to the integration of platform-type studies that incorporate novel statistical design, leading to expediencies in drug development, timelines, cost and other resources. Platform studies enable parallel investigation of multiple novel agents, with early signal adjudication of success or failure to allow efficient signal seeking. |
| Keywords: | long-term; growth-factor receptor; phase-iii trial; nab-paclitaxel; ductal adenocarcinoma; open-label; t-cell immunity; tumor-infiltrating macrophages; term survivors; adjuvant gemcitabine |
| Journal Title: | Nature Reviews Gastroenterology & Hepatology |
| ISSN: | 1759-5045 |
| Publisher: | Nature Publishing Group |
| Publication status: | Online ahead of print |
| Date Published: | 2023-01-01 |
| Online Publication Date: | 2023-01-01 |
| Language: | English |
| ACCESSION: | WOS:001076186400001 |
| DOI: | 10.1038/s41575-023-00840 |
| PROVIDER: | wos |
| Notes: | Review; Early Access -- Source: Wos |
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