Our Oncology research focuses on discovering mechanism-based therapeutics targeted to the right patients with the ultimate goal of improving the survival and quality of life of cancer patients around the world. Novartis has a long-standing commitment to oncology research and has a diverse and robust research portfolio. Current therapeutic approaches target the pathogenic molecular mechanisms in cancer including genetic dependence (such as PI3K, ABL, BRAF, SMO, CDK4), lineage dependence (such as Wnt signaling, PRLR), stromal dependence (such as CSF1), and empiric dependence or “synthetic lethality” (such as HSP90).
The Oncology research efforts span a wide-variety of tumors including common tumors such as breast and lung cancer as well as rare tumor types including medulloblastoma and sarcomas. In addition, significant efforts are now being made to understand specific mechanisms of therapeutic resistance with the goal of creating best-in-class molecules. This focus on resistance is also naturally linked to our efforts to identify highly effective novel drug combinations.
Protein kinase C inhibitor sotrastaurin selectively inhibits the growth of CD79 mutant diffuse large B-cell lymphomas. Naylor TL, Tang H, Ratsch BA, Enns A, Loo A, Chen L, Lenz P, Waters NJ, Schuler W, Dörken B, Yao YM, Warmuth M, Lenz G, Stegmeier F. Cancer Res. 2011 Apr 1;71(7):2643-53. Epub 2011 Feb 15.
Loss of the tumor suppressor Snf5 leads to aberrant activation of the Hedgehog-Gli pathway. Jagani Z, Mora-Blanco EL, Sansam CG, McKenna ES, Wilson B, Chen D, Klekota J, Tamayo P, Nguyen PT, Tolstorukov M, Park PJ, Cho YJ, Hsiao K, Buonamici S, Pomeroy SL, Mesirov JP, Ruffner H, Bouwmeester T, Luchansky SJ, Murtie J, Kelleher JF, Warmuth M, Sellers WR, Roberts CW, Dorsch M. Nat Med. 2010 Dec;16(12):1429-33. Epub 2010 Nov 14.
Identification and structure-activity relationship of 2-morpholino 6-(3-hydroxyphenyl) pyrimidines, a class of potent and selective PI3 kinase inhibitors. Pecchi S, Renhowe PA, Taylor C, Kaufman S, Merritt H, Wiesmann M, Shoemaker KR, Knapp MS, Ornelas E, Hendrickson TF, Fantl W, Voliva CF. Bioorg Med Chem Lett. 2010 Dec 1;20(23):6895-8. Epub 2010 Oct 13.