KRAS G12C Inhibition in Non-Small Cell Lung Cancer
Targeting KRAS is one of cancer’s greatest challenges1

KRASG12C inhibition is an attractive target in NSCLC2

There remains a high unmet need in the treatment of 2L patients with NSCLC3

For patients without actionable mutations who progress on 1L immunotherapy/chemotherapy, there is an unmet need for additional 2L options.4

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patients receive only supportive care in 2L, potentially due to more advanced disease, comorbidities, and poor performance status5,6
patients receive only supportive care in 2L, potentially due to more advanced disease, comorbidities, and poor performance status5,6

The KRAS G12C mutation drives cancer cell growth and survival2

KRAS G12C is a point mutation at codon 12 that causes a glycine to cysteine amino acid substitution.7

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KRASG12C inhibition is an attractive target and warrants further investigation in NSCLC2

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TOGGLE between KRASG12C oncogenic signaling and inhibition2,8-10

  • In normal cells, KRAS cycles between an active and inactive state to regulate downstream signaling pathways, leading to cellular proliferation, differentiation, and survival2,11-13
  • In tumor cells, the active GTP-bound form of KRASG12C is favored, resulting in oncogenic signaling and tumorigenesis2,9
  • Covalent inhibitors are under investigation with the potential to specifically and irreversibly bind to cysteine-12, locking KRASG12C in the inactive state without affecting wild-type signaling8,14

Watch the video below for a deeper look into the role of KRAS G12C in cancer

Inhibition of KRASG12C represents an important approach in NSCLC, which warrants further investigation

1L, first line; 2L, second line; AKT, protein kinase B; EGFR, epidermal growth factor receptor; ERK, extracellular signal-regulated kinase; GDP, guanosine diphosphate; GTP, guanosine triphosphate; KRAS, Kirsten rat sarcoma; MEK, mitogen-activated protein kinase kinase; mTOR, mammalian target of rapamycin; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; NSCLC, non-small cell lung cancer; PI3K, phosphoinositide 3-kinase; RAF, rapidly accelerated fibrosarcoma; RAL, Ras-like; RTK, receptor tyrosine kinase.

References: 1. Cox AD, et al. Nat Rev Drug Discov. 2014;13:828-851. 2. Ryan MB, et al. Nat Rev Clin Oncol. 2018;15:709-720. 3. Nadler E, et al. Clin Lung Cancer. 2018;19:360-370. 4. Santos ES, et al. Expert Rev Anticancer Ther. 2020;20:221-228. 5. Ruppert A-M, et al. JTO Clin Res Rep. 2020. doi:10.1016/j/jtocrr.2020.100052. 6. Kitazawa H, et al. Sci Rep. 2019;9:19872. 7. Ihle NT, et al. J Natl Cancer Inst. 2012;104:228-239. 8. Canon J, et al. Nature. 2019;575:217-223. 9. Neel NF, et al. Genes Cancer. 2011;2:275-287. 10. Ferrer I, et al. Lung Cancer. 2018;124:53-64. 11. Simanshu DK, et al. Cell. 2017;170:17-33. 12. Barbacid M. Annu Rev Biochem. 1987;56:779-827. 13. Román M, et al. Mol Cancer. 2018;17:33. 14. Ostrem JML, et al. Nat Rev Drug Discov. 2016;15:771-785.