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KRAS-Mutated Lung Cancer

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Targeted Therapies for Lung Cancer

Part of the book series: Current Cancer Research ((CUCR))

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Abstract

A mutation in the Kirsten rat sarcoma virus transforming protein (KRAS) is the most common genomic driver identified in patients with lung adenocarcinoma. It is a key component of the PI3K and MAPK pathways and is an important regulator of cell proliferation and survival. Tobacco use and mutations in KRAS are strongly correlated and co-mutation of p53 or STK11 is common. KRAS is affected by upstream signaling from a variety of tyrosine kinase inhibitors including the epidermal growth factor receptor (EGFR) and ERBB2. Affected patients have a higher risk of death than with other driver mutations and, despite dozens of clinical trials attempting to find a specific inhibitor that is effective in this population, it has been a difficult drug target. There is substantial experience attempting to treat KRAS-mutated lung adenocarcinoma with the use of RAS/RAF multikinase inhibitors as well as inhibitors of both upstream and downstream proteins important in RAS signaling. We review the disappointing results from these clinical trials in lung cancer. However, more recently, there appears to be some improvement in outcome with immune checkpoint inhibitors in these patients.

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References

  1. Tsuchida N, Ryder T, Ohtsubo E. Nucleotide sequence of the oncogene encoding the p21 transforming protein of Kirsten murine sarcoma virus. Science. 1982;217(4563):937–9.

    Article  CAS  PubMed  Google Scholar 

  2. Chen Y, McGee J, Chen X, et al. Identification of druggable cancer driver genes amplified across TCGA datasets. PLoS One. 2014;9(5):e98293.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Westcott PM, To MD. The genetics and biology of KRAS in lung cancer. Chin J Cancer. 2013;32(2):63–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Reuter CW, Morgan MA, Bergmann L. Targeting the Ras signaling pathway: a rational, mechanism-based treatment for hematologic malignancies? Blood. 2000;96(5):1655–69.

    CAS  PubMed  Google Scholar 

  5. Zebisch A, Troppmair J. Back to the roots: the remarkable RAF oncogene story. Cell Mol Life Sci. 2006;63(11):1314–30.

    Article  CAS  PubMed  Google Scholar 

  6. Jirmanova L, Afanassieff M, Gobert-Gosse S, Markossian S, Savatier P. Differential contributions of ERK and PI3-kinase to the regulation of cyclin D1 expression and to the control of the G1/S transition in mouse embryonic stem cells. Oncogene. 2002;21(36):5515–28.

    Article  CAS  PubMed  Google Scholar 

  7. Pierre S, Bats AS, Coumoul X. Understanding SOS (Son of Sevenless). Biochem Pharmacol. 2011;82(9):1049–56.

    Article  CAS  PubMed  Google Scholar 

  8. Sadidi M, Lentz SI, Feldman EL. Hydrogen peroxide-induced Akt phosphorylation regulates Bax activation. Biochimie. 2009;91(5):577–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Zhang X, Tang N, Hadden TJ, Rishi AK. Akt, FoxO and regulation of apoptosis. Biochim Biophys Acta. 2011;1813(11):1978–86.

    Article  CAS  PubMed  Google Scholar 

  10. Lowenstein EJ, Daly RJ, Batzer AG, et al. The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling. Cell. 1992;70(3):431–42.

    Article  CAS  PubMed  Google Scholar 

  11. Giaccone G, Gallegos Ruiz M, Le Chevalier T, et al. Erlotinib for frontline treatment of advanced non-small cell lung cancer: a phase II study. Clin Cancer Res. 2006;12(20 Pt 1):6049–55.

    Article  CAS  PubMed  Google Scholar 

  12. Pao W, Wang TY, Riely GJ, et al. KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med. 2005;2(1):e17.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Siddiqui AD, Piperdi B. KRAS mutation in colon cancer: a marker of resistance to EGFR-I therapy. Ann Surg Oncol. 2010;17(4):1168–76.

    Article  PubMed  Google Scholar 

  14. Bockorny B, Rusan M, Chen W, et al. RAS-MAPK reactivation facilitates acquired resistance in FGFR1-amplified lung cancer and underlies a rationale for upfront FGFR-MEK blockade. Mol Cancer Ther. 2018.

    Google Scholar 

  15. Desai A, Adjei AA. FGFR signaling as a target for lung cancer therapy. J Thorac Oncol. 2016;11(1):9–20.

    Article  PubMed  Google Scholar 

  16. Hashemi-Sadraei N, Hanna N. Targeting FGFR in squamous cell carcinoma of the lung. Target Oncol. 2017;12(6):741–55.

    Article  PubMed  Google Scholar 

  17. Ugocsai K, Mandoky L, Tiszlavicz L, Molnar J. Investigation of HER2 overexpression in non-small cell lung cancer. Anticancer Res. 2005;25(4):3061–6.

    CAS  PubMed  Google Scholar 

  18. Shigematsu H, Takahashi T, Nomura M, et al. Somatic mutations of the HER2 kinase domain in lung adenocarcinomas. Cancer Res. 2005;65(5):1642–6.

    Article  CAS  PubMed  Google Scholar 

  19. Salgia R. MET in lung cancer: biomarker selection based on scientific rationale. Mol Cancer Ther. 2017;16(4):555–65.

    Article  CAS  PubMed  Google Scholar 

  20. Leiser D, Medova M, Mikami K, et al. KRAS and HRAS mutations confer resistance to MET targeting in preclinical models of MET-expressing tumor cells. Mol Oncol. 2015;9(7):1434–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Gainor JF, Varghese AM, Ou SH, et al. ALK rearrangements are mutually exclusive with mutations in EGFR or KRAS: an analysis of 1683 patients with non-small cell lung cancer. Clin Cancer Res. 2013;19(15):4273–81.

    Article  CAS  PubMed  Google Scholar 

  22. Hrustanovic G, Bivona TG. RAS signaling in ALK fusion lung cancer. Small GTPases. 2016;7(1):32–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Ambrogio C, Nadal E, Villanueva A, et al. KRAS-driven lung adenocarcinoma: combined DDR1/Notch inhibition as an effective therapy. ESMO Open. 2016;1(5):e000076.

    Article  PubMed  PubMed Central  Google Scholar 

  24. 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(5324):333–8.

    Article  CAS  PubMed  Google Scholar 

  25. Cancer Genome Atlas Research N. Comprehensive molecular profiling of lung adenocarcinoma. Nature. 2014;511(7511):543–50.

    Article  CAS  Google Scholar 

  26. El-Osta B, Behera M, Kim S, et al. Characteristics and outcomes of patients (pts) with metastatic KRAS mutant lung adenocarcinomas: lung cancer mutation consortium (LCMC) database. ASCO Annual Meet. 2017; 2017; Chicago: JCO; 2017.

    Google Scholar 

  27. Quinlan MP, Settleman J. Isoform-specific ras functions in development and cancer. Future Oncol. 2009;5(1):105–16.

    Article  CAS  PubMed  Google Scholar 

  28. Sun Y, Ren Y, Fang Z, et al. Lung adenocarcinoma from East Asian never-smokers is a disease largely defined by targetable oncogenic mutant kinases. J Clin Oncol. 2010;28(30):4616–20.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Riely GJ, Kris MG, Rosenbaum D, et al. Frequency and distinctive spectrum of KRAS mutations in never smokers with lung adenocarcinoma. Clinical Cancer Res. 2008;14(18):5731–4.

    Article  CAS  Google Scholar 

  30. Smits AJ, Kummer JA, Hinrichs JW, et al. EGFR and KRAS mutations in lung carcinomas in the Dutch population: increased EGFR mutation frequency in malignant pleural effusion of lung adenocarcinoma. Cell Oncol (Dordr). 2012;35(3):189–96.

    Article  CAS  Google Scholar 

  31. Dogan S, Shen R, Ang DC, et al. Molecular epidemiology of EGFR and KRAS mutations in 3026 lung adenocarcinomas: higher susceptibility of women to smoking-related KRAS-mutant cancers. Clinical Cancer Res. 2012;18(22):6169–77.

    Article  CAS  Google Scholar 

  32. Mascaux C, Iannino N, Martin B, et al. The role of RAS oncogene in survival of patients with lung cancer: a systematic review of the literature with meta-analysis. Br J Cancer. 2005;92(1):131–9.

    Article  CAS  PubMed  Google Scholar 

  33. Schiller JH, Adak S, Feins RH, et al. Lack of prognostic significance of p53 and K-ras mutations in primary resected non-small-cell lung cancer on E4592: a laboratory ancillary study on an eastern cooperative oncology group prospective randomized trial of postoperative adjuvant therapy. J Clin Oncol. 2001;19(2):448–57.

    Article  CAS  PubMed  Google Scholar 

  34. Winton T, Livingston R, Johnson D, et al. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. New England J Med. 2005;352(25):2589–97.

    Article  CAS  Google Scholar 

  35. Scoccianti C, Vesin A, Martel G, et al. Prognostic value of TP53, KRAS and EGFR mutations in nonsmall cell lung cancer: the EUELC cohort. Eur Respir J. 2012;40(1):177–84.

    Article  CAS  PubMed  Google Scholar 

  36. Skoulidis F, Byers LA, Diao L, et al. Co-occurring genomic alterations define major subsets of KRAS-mutant lung adenocarcinoma with distinct biology, immune profiles, and therapeutic vulnerabilities. Cancer Discov. 2015;5(8):860–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Maeda Y, Tsuchiya T, Hao H, et al. Kras(G12D) and Nkx2–1 haploinsufficiency induce mucinous adenocarcinoma of the lung. J Clin Invest. 2012;122(12):4388–400.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Snyder EL, Watanabe H, Magendantz M, et al. Nkx2–1 represses a latent gastric differentiation program in lung adenocarcinoma. Mol Cell. 2013;50(2):185–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Ihle NT, Byers LA, Kim ES, et al. Effect of KRAS oncogene substitutions on protein behavior: implications for signaling and clinical outcome. J Natl Cancer Inst. 2012;104(3):228–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Park S, Kim JY, Lee SH, et al. KRAS G12C mutation as a poor prognostic marker of pemetrexed treatment in non-small cell lung cancer. Korean J Intern Med. 2017;32(3):514–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Shepherd FA, Lacas B, Le Teuff G, et al. Pooled analysis of the prognostic and predictive effects of TP53 comutation status combined with KRAS or EGFR mutation in early-stage resected non-small-cell lung cancer in four trials of adjuvant chemotherapy. J Clin Oncol. 2017;35(18):2018–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Tomasini P, Walia P, Labbe C, Jao K, Leighl NB. Targeting the KRAS pathway in non-small cell lung cancer. Oncologist. 2016;21(12):1450–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Janes MR, Zhang J, Li LS, et al. Targeting KRAS mutant cancers with a covalent G12C-specific inhibitor. Cell. 2018;172(3):578–89.e17.

    Article  CAS  PubMed  Google Scholar 

  44. Statsyuk AV. Let K-Ras activate its own inhibitor. Nat Struct Mol Biol. 2018.

    Google Scholar 

  45. Smit EF, Dingemans AM, Thunnissen FB, Hochstenbach MM, van Suylen RJ, Postmus PE. Sorafenib in patients with advanced non-small cell lung cancer that harbor K-ras mutations: a brief report. J Thorac Oncol. 2010;5(5):719–20.

    Article  PubMed  Google Scholar 

  46. David Michael Waterhouse DMS, Davey B. Daniel, Paula L. Griner, F Anthony Greco, Howard A. Burris, John D. Hainsworth, David R. Spigel KRAS subset analysis from randomized phase II trials of erlotinib versus erlotinib plus sorafenib or pazopanib in refractory non-small cell lung cancer (NSCLC). JCO. 2013;31.

    Google Scholar 

  47. David S, Hong AH, Gordon MS, Flaherty KT, Shapiro G, Rodon J, Millward M, Ramdas N, Zhang W, Gao L, Sykes A, Willard MD, Yu D, Schade A, Flynn DL, Kaufman M, Peng S-B, Conti I, Tiu RV, Sullivan RJ. A first-in-human dose phase 1 study of LY3009120 in advanced cancer patients. JCO. Chicago 2017.

    Google Scholar 

  48. Janku F, Iyer G, Spreafico A, et al. A phase I study of LXH254 in patients (pts) with advanced solid tumors harboring MAPK pathway alterations. J Clin Oncol. 2018;36(15_suppl):2586.

    Article  Google Scholar 

  49. Riely GJ, Johnson ML, Medina C, et al. A phase II trial of Salirasib in patients with lung adenocarcinomas with KRAS mutations. J Thorac Oncol. 2011;6(8):1435–7.

    Article  PubMed  Google Scholar 

  50. Carter CA, Rajan A, Keen C, et al. Selumetinib with and without erlotinib in KRAS mutant and KRAS wild-type advanced nonsmall-cell lung cancer. Ann Oncol. 2016;27(4):693–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Blumenschein GR, Smit EF, Planchard D, et al. MEK114653: a randomized, multicenter, phase II study to assess efficacy and safety of trametinib (T) compared with docetaxel (D) in KRAS-mutant advanced non–small cell lung cancer (NSCLC). J Clin Oncol. 2013;31(15_suppl):8029.

    Google Scholar 

  52. Gandara DR, Leighl N, Delord JP, et al. A phase 1/1b study evaluating trametinib plus docetaxel or pemetrexed in patients with advanced non-small cell lung cancer. J Thorac Oncol. 2017;12(3):556–66.

    Article  PubMed  Google Scholar 

  53. Chenard-Poirier M, Kaiser M, Boyd K, et al. Results from the biomarker-driven basket trial of RO5126766 (CH5127566), a potent RAF/MEK inhibitor, in RAS- or RAF-mutated malignancies including multiple myeloma. J Clin Oncol. 2017;35(15_suppl):2506.

    Article  Google Scholar 

  54. Sequist LV, Jv P, Garmey EG, et al. Randomized phase II study of erlotinib plus tivantinib versus erlotinib plus placebo in previously treated non–small-cell lung cancer. J Clin Oncol. 2011;29(24):3307–15.

    Article  CAS  PubMed  Google Scholar 

  55. Gerber DE, Socinski MA, Neal JW, et al. Randomized phase 2 study of tivantinib plus erlotinib versus single-agent chemotherapy in previously treated KRAS mutant advanced non-small cell lung cancer. Lung Cancer. 2018;117:44–9.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Spigel DR, Ervin TJ, Ramlau RA, et al. Randomized phase II trial of Onartuzumab in combination with erlotinib in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2013;31(32):4105–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Jiang ZB, Huang J, Xie C, et al. Combined use of PI3K and MEK inhibitors synergistically inhibits lung cancer with EGFR and KRAS mutations. Oncol Rep. 2016;36(1):365–75.

    Article  CAS  PubMed  Google Scholar 

  58. Vansteenkiste JF, Canon JL, De Braud F, et al. Safety and efficacy of Buparlisib (BKM120) in patients with PI3K pathway-activated non-small cell lung cancer: results from the phase II BASALT-1 study. J Thorac Oncol. 2015;10(9):1319–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. O’Donnell A, Faivre S, Judson I, et al. A phase I study of the oral mTOR inhibitor RAD001 as monotherapy to identify the optimal biologically effective dose using toxicity, pharmacokinetic (PK) and pharmacodynamic (PD) endpoints in patients with solid tumors. Proc Am Soc Clin Oncol. 2003;2003:200.

    Google Scholar 

  60. Owonikoko TK, Ramalingam SS, Miller DL, et al. A translational, pharmacodynamic, and pharmacokinetic phase IB clinical study of everolimus in resectable non-small cell lung cancer. Clin Cancer Res. 2015;21(8):1859–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Price KA, Azzoli CG, Krug LM, et al. Phase II trial of gefitinib and everolimus in advanced non-small cell lung cancer. J Thorac Oncol. 2010;5(10):1623–9.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Nogova L, Mattonet C, Gardizi M, et al. SORAVE: Sorafenib and everolimus for treatment of patients with relapsed solid tumors and with KRAS mutated NSCLC—a phase I study. J Clin Oncol. 2013;31(15_suppl):8112.

    Google Scholar 

  63. Heist RS, Gandhi L, Shapiro G, et al. Combination of a MEK inhibitor, pimasertib (MSC1936369B), and a PI3K/mTOR inhibitor, SAR245409, in patients with advanced solid tumors: Results of a phase Ib dose-escalation trial. Am Soc Clin Oncol. 2013.

    Google Scholar 

  64. Janne PA, Cohen RB, Laird AD, et al. Phase I safety and pharmacokinetic study of the PI3K/mTOR inhibitor SAR245409 (XL765) in combination with erlotinib in patients with advanced solid tumors. J Thorac Oncol. 2014;9(3):316–23.

    Article  PubMed  CAS  Google Scholar 

  65. Riely GJ, Brahmer JR, Planchard D, et al. A randomized discontinuation phase II trial of ridaforolimus in non-small cell lung cancer (NSCLC) patients with KRAS mutations. J Clin Oncol. 2012;30(15_suppl):7531.

    Google Scholar 

  66. Peters S, Gettinger S, Johnson ML, et al. Phase II trial of atezolizumab as first-line or subsequent therapy for patients with programmed death-ligand 1-selected advanced non-small-cell lung cancer (BIRCH). J Clin Oncol. 2017;35(24):2781–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Kim JH, Kim HS, Kim BJ. Prognostic value of KRAS mutation in advanced non-small-cell lung cancer treated with immune checkpoint inhibitors: a meta-analysis and review. Oncotarget. 2017;8(29):48248–52.

    PubMed  PubMed Central  Google Scholar 

  68. Goldman JW, Mazieres J, Barlesi F, et al. A randomized phase 3 study of abemaciclib versus erlotinib in previously treated patients with stage IV NSCLC with KRAS mutation: JUNIPER. J Clin Oncol. 2018;36(15_suppl):9025.

    Article  Google Scholar 

  69. Ramalingam S, Goss G, Rosell R, et al. A randomized phase II study of ganetespib, a heat shock protein 90 inhibitor, in combination with docetaxel in second-line therapy of advanced non-small cell lung cancer (GALAXY-1). Ann Oncol. 2015;26(8):1741–8.

    Article  CAS  PubMed  Google Scholar 

  70. Riely GJ, Gettinger SN, Stoller RG, et al. Safety and activity of IPI-504 (retaspimycin hydrochloride) and docetaxel in pretreated patients (pts) with metastatic non-small cell lung cancer (NSCLC). J Clin Oncol. 2011;29(15_suppl):7516.

    Article  Google Scholar 

  71. Schlaepfer DD, Hunter T. Focal adhesion kinase overexpression enhances ras-dependent integrin signaling to ERK2/mitogen-activated protein kinase through interactions with and activation of c-Src. J Biol Chem. 1997;272(20):13189–95.

    Article  CAS  PubMed  Google Scholar 

  72. Gerber DE, Ramalingam SS, Morgensztern D, et al. A phase 2 study of defactinib (VS-6063), a cancer stem cell inhibitor that acts through inhibition of focal adhesion kinase (FAK), in patients with KRAS-mutant non-small cell lung cancer. J Clin Oncol. 2014;32(15_suppl):TPS8126–TPS.

    Article  Google Scholar 

  73. Yamada T, Amann JM, Tanimoto A, et al. Histone deacetylase inhibition enhances the antitumor activity of a MEK inhibitor in lung cancer cells harboring RAS mutations. Mol Cancer Ther. 2018;17(1):17–25.

    Article  CAS  PubMed  Google Scholar 

  74. Gerber DE, Boothman DA, Fattah FJ, et al. Phase 1 study of romidepsin plus erlotinib in advanced non-small cell lung cancer. Lung Cancer. 2015;90(3):534–41.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Dean EJ, Falchook GS, Patel MR, et al. Preliminary activity in the first in human study of the first-in-class fatty acid synthase (FASN) inhibitor, TVB-2640. J Clin Oncol. 2016;34(15_suppl):2512.

    Article  Google Scholar 

  76. Litvak AM, Drilon AE, Rekhtman N, et al. Phase II trial of bortezomib in KRAS G12D mutant lung cancers. J Clin Oncol. 2015;33(15_suppl):e19002–e.

    Article  Google Scholar 

  77. Adjei AA, Erlichman C, Davis JN, et al. A Phase I trial of the farnesyl transferase inhibitor SCH66336: evidence for biological and clinical activity. Cancer Res. 2000;60(7):1871–7.

    CAS  PubMed  Google Scholar 

  78. Khuri FR, Glisson BS, Kim ES, et al. Phase I study of the farnesyltransferase inhibitor lonafarnib with paclitaxel in solid tumors. Clin Cancer Res. 2004;10(9):2968–76.

    Article  CAS  PubMed  Google Scholar 

  79. Kim ES, Kies MS, Fossella FV, et al. Phase II study of the farnesyltransferase inhibitor lonafarnib with paclitaxel in patients with taxane-refractory/resistant nonsmall cell lung carcinoma. Cancer. 2005;104(3):561–9.

    Article  CAS  PubMed  Google Scholar 

  80. Blumenschein GR, Khuri F, Gatzemeier U, et al. A randomized phase III trial comparing bexarotene/carboplatin/paclitaxel versus carboplatin/paclitaxel in chemotherapy-naive patients with advanced or metastatic non-small cell lung cancer (NSCLC). J Clin Oncol. 2005;23(16_suppl):LBA7001–LBA.

    Article  Google Scholar 

  81. Adjei AA, Mauer A, Bruzek L, et al. Phase II study of the farnesyl transferase inhibitor R115777 in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2003;21(9):1760–6.

    Article  CAS  PubMed  Google Scholar 

  82. Yang SH, Baek HA, Lee HJ, et al. Discoidin domain receptor 1 is associated with poor prognosis of non-small cell lung carcinomas. Oncol Rep. 2010;24(2):311–9.

    CAS  PubMed  Google Scholar 

  83. Fong KM, Zimmerman PV, Smith PJ. KRAS codon 12 mutations in Australian non-small cell lung cancer. Aust N Z J Med. 1998;28(2):184–9.

    Article  CAS  PubMed  Google Scholar 

  84. Tam IY, Chung LP, Suen WS, et al. Distinct epidermal growth factor receptor and KRAS mutation patterns in non-small cell lung cancer patients with different tobacco exposure and clinicopathologic features. Clin Cancer Res. 2006;12(5):1647–53.

    Article  CAS  PubMed  Google Scholar 

  85. Zheng D, Wang R, Zhang Y, et al. The prevalence and prognostic significance of KRAS mutation subtypes in lung adenocarcinomas from Chinese populations. Onco Targets Ther. 2016;9:833–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Boch C, Kollmeier J, Roth A, et al. The frequency of EGFR and KRAS mutations in non-small cell lung cancer (NSCLC): routine screening data for central Europe from a cohort study. BMJ Open. 2013;3(4).

    Article  PubMed  PubMed Central  Google Scholar 

  87. Brose MS, Volpe P, Feldman M, et al. BRAF and RAS mutations in human lung cancer and melanoma. Cancer Res. 2002;62(23):6997–7000.

    CAS  PubMed  Google Scholar 

  88. Rodenhuis S, Slebos RJ, Boot AJ, et al. Incidence and possible clinical significance of K-ras oncogene activation in adenocarcinoma of the human lung. Cancer Res. 1988;48(20):5738–41.

    CAS  PubMed  Google Scholar 

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  1. Department of Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA

    Arnab Basu & Jorge Nieva

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  1. Arnab Basu
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  2. Jorge Nieva
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  1. Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA, USA

    Ravi Salgia

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Basu, A., Nieva, J. (2019). KRAS-Mutated Lung Cancer. In: Salgia, R. (eds) Targeted Therapies for Lung Cancer. Current Cancer Research. Springer, Cham. https://doi.org/10.1007/978-3-030-17832-1_10

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