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Targeting RAS in PDAC

CE / CME

Novel RAS-Targeted Therapies for Pancreatic Ductal Adenocarcinoma

ABIM MOC: maximum of 0.75 Medical Knowledge MOC point

Physicians: Maximum of 0.75 AMA PRA Category 1 Credit

Released: April 15, 2026

Expiration: October 14, 2026

Activity

Progress
1 2 3
Course Completed

References

  1. Hu J, Zhao G, Wang H, et al. The role of KRAS in pancreatic cancer: from bench to bedside. World J Gastroenterol. 2021;27:4298-4311.
  2. American Cancer Society. Cancer stat facts: pancreatic cancer 2026. cancer.org. Accessed April 9, 2026.
  3. Siegel RL, Miller KD, Wagle NS, et al. Cancer statistics, 2024. CA Cancer J Clin. 2024;74:12-49.
  4. Cancer Genome Atlas Research Network. Integrated genomic characterization of pancreatic ductal adenocarcinoma. Cancer Cell. 2017;32:185-203.
  5. National Comprehensive Cancer Network. Clinical practice guidelines in oncology: pancreatic adenocarcinoma. v1.2026. nccn.org. Accessed April 9, 2026.
  6. Norton JW, Patel NM, Smith LM, et al. Trends in pancreatic cancer incidence and mortality in the United States, 2001-2021. JAMA Netw Open. 2025;8:e2453588.
  7. Singhal M, Toste PA, et al. Targeting KRAS in pancreatic cancer. Nat Med. 2024;30:969-979.
  8. Scheffzek K, Ahmadian MR, Kabsch W, et al. The Ras–RasGAP complex: structural basis for GTPase activation and its loss in oncogenic Ras mutants. Science. 1997;277:333-338.
  9. Hunter J C, Gurbani D, Ficarro S B, et al. In situ selectivity profiling and crystal structure of SML-8-73-1, an active site inhibitor of oncogenic K-Ras G12C. Mol Cancer Res. 2015;13:1325-1335.
  10. Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364:1817-1825.
  11. Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369:1691-1703.
  12. Wainberg ZA, Melisi D, Macarulla T, et al. NALIRIFOX versus nab-paclitaxel plus gemcitabine in patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial. Lancet. 2023;402:1272-1281.
  13. Golan TD, Hammel P, Reni M, et al. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. N Engl J Med. 2019;381:317-327.
  14. Kindler HL, Hammel P, Reni M, et al. Overall survival results from the POLO trial: a phase III study of active maintenance olaparib versus placebo for germline BRCA-Mutated metastatic pancreatic cancer. J Clin Oncol. 2022;40:3929-3939.
  15. Schram AM, Odintsov IM, Chiang DY, et al. Tumor-agnostic activity of KRAS G12C inhibition. N Engl J Med. 2025;392:566-577.
  16. Strickler JH, Satake H, George TJ, et al. Sotorasib in KRAS p.G12C–mutated advanced pancreatic cancer. N Engl J Med. 2023;388:33-43.
  17. Bekaii-Saab TS, Spira AI, Yaeger R, et al. KRYSTAL-1: Updated activity and safety of adagrasib (MRTX849) in patients (Pts) with unresectable or metastatic pancreatic cancer (PDAC) and other gastrointestinal (GI) tumors harboring a KRAS G12C mutation. Presented at: 2022 ASCO Gastrointestinal Cancers Symposium; January 20-22, 2022. Abstract 519.
  18. Riedl JM, Dreyer SB, Jamieson NB, et al. Targeting KRAS alterations in pancreatic cancer: emerging therapeutic strategies. Cancer Cell. 2026;44:471-485.
  19. Cox AD, Fesik SW, Kimmelman AC, et al. Drugging the undruggable RAS: recent advances and future directions. Science. 2024;385:1274-1280.
  20. Varghese AM, Yaeger R, O'Reilly EM, et al. KRAS-targeted therapies in pancreatic cancer. Nat Med. 2025;31:466-476.
  21. Tabernero J, Lenz HJ, Siena S, et al. First-in-human study of a KRAS G12C inhibitor in advanced solid tumors. J Clin Oncol. 2021;39:273-284.
  22. Elez E, Fakih M, Strickler JH, et al. Clinical activity of KRAS-targeted therapy in gastrointestinal cancers. N Engl J Med. 2025;392:2425-2436.
  23. Spira A, Papadopoulos K, Kim D, et al. Preliminary safety, antitumor activity, and circulating tumor DNA (ctDNA) changes with RMC-9805, an oral, RAS(ON) G12D-selective tri-complex inhibitor in patients with KRAS G12D pancreatic ductal adenocarcinoma (PDAC) from a phase 1 study in advanced solid tumors. J Clin Oncol. 2025;43(4):724.
  24. Zhou S, Li Z, Sun Y, et al. Efficacy and safety of GFH375 monotherapy in previously treated advanced KRAS G12D-mutant pancreatic ductal adenocarcinoma (PDAC). Presented at: 2025 European Society for Medical Oncology Congress; September 2025. Abstract LBA84.
  25. Wang L, Jiang K, Li W, et al. HRS-4642 combined with gemcitabine and nab-paclitaxel in KRAS-G12D mutant advanced pancreatic cancer: A phase Ib/II study. Presented at: 2025 European Society for Medical Oncology Congress; September 2025. Abstract 2215O.
  26. Wainberg ZA, Henry JT, Park H, et al. Preliminary phase 1 results of INCB161734, a novel oral Kirsten rat sarcoma (KRAS) G12D inhibitor, as monotherapy or in combination with chemotherapy for advanced/metastatic pancreatic duct adenocarcinoma (PDAC). Presented at: 2026 ASCO Gastrointestinal Cancers Symposium; January 12, 2026. Abstract 654.
  27. Li J, Fu S, Spira A, et al. Updated results of the phase 1/2 study of TSN1611, a highly selective KRAS G12D inhibitor, in patients with advanced solid tumors. Presented at: 2026 ASCO Gastrointestinal Cancers Symposium; January 9, 2026. Abstract 710.
  28. Park K, Kasi A, Spira AI, et al. Setidegrasib in advanced non–small-cell lung cancer and pancreatic cancer. N Engl J Med. 2026;394:1409-1420 .
  29. Pant S, Wainberg ZA, Weekes CD, et al. Lymph node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: the phase 1 AMPLIFY-201 trial. Nat Med. 2024;30:531-542.
  30. Wainberg ZA, Weekes CD, Furqan M, et al. Lymph node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: phase 1 AMPLIFY-201 trial final results. Nat Med. 2025;31:3648-3653.