Abstract 340: Predictive value of KRAS mutations in advanced non-small cell lung cancer (NSCLC) patients (pts) treated with chemotherapy (CT)

Author(s):  
Anne-Marie C. Dingemans ◽  
Egbert F. Smit ◽  
Jules Derks ◽  
Wouter Mellema ◽  
Danielle Heideman ◽  
...  
2012 ◽  
Vol 18 (3 Supplement) ◽  
pp. A31-A31
Author(s):  
Wouter W. Mellema ◽  
Anne-Marie C. Dingemans ◽  
Egbert F. Smit ◽  
Jules Derks ◽  
Daniëlle A.M. Heideman ◽  
...  

PLoS ONE ◽  
2013 ◽  
Vol 8 (5) ◽  
pp. e64816 ◽  
Author(s):  
Jong-Mu Sun ◽  
Deok Won Hwang ◽  
Jin Seok Ahn ◽  
Myung-Ju Ahn ◽  
Keunchil Park

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5956
Author(s):  
Noriaki Sunaga ◽  
Yosuke Miura ◽  
Norimitsu Kasahara ◽  
Reiko Sakurai

Recent advances in molecular biology and the resultant identification of driver oncogenes have achieved major progress in precision medicine for non-small-cell lung cancer (NSCLC). v-Ki-ras2 Kirsten rat sarcoma viral oncogene (KRAS) is the most common driver in NSCLC, and targeting KRAS is considerably important. The recent discovery of covalent KRAS G12C inhibitors offers hope for improving the prognosis of NSCLC patients, but the development of combination therapies corresponding to tumor characteristics is still required given the vast heterogeneity of KRAS-mutated NSCLC. In this review, we summarize the current understanding of KRAS mutations regarding the involvement of malignant transformation and describe the preclinical and clinical evidence for targeting KRAS-mutated NSCLC. We also discuss the mechanisms of resistance to KRAS G12C inhibitors and possible combination treatment strategies to overcome this drug resistance.


2016 ◽  
Vol 5 (5) ◽  
pp. 511-516 ◽  
Author(s):  
Mónica Garzón ◽  
Sergi Villatoro ◽  
Cristina Teixidó ◽  
Clara Mayo ◽  
Alejandro Martínez ◽  
...  

2017 ◽  
Vol 12 (11) ◽  
pp. S2085-S2086 ◽  
Author(s):  
D. Cronin-Fenton ◽  
T. Dalvi ◽  
E. Hedgeman ◽  
M. Norgaard ◽  
L. Petersen ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Deirdre Cronin-Fenton ◽  
Tapashi Dalvi ◽  
Naimisha Movva ◽  
Lars Pedersen ◽  
Hanh Hansen ◽  
...  

AbstractProgrammed cell death receptor ligand-1 (PD-L1) expression, KRAS (KRASm) and EGFR (EGFRm) mutations may influence non-small cell lung cancer (NSCLC) prognosis. We aimed to evaluate PD-L1 expression, KRASm, and EGFRm and survival among stage III unresected NSCLC patients. Using Danish registries, we collected data on stage III unresected NSCLC patients diagnosed 2001–2012 and paraffin-embedded tumor tissue from pathology archives. We assessed PD-L1 expression in tumors and tumor-infiltrating immune cells (ICs) by immunohistochemistry ($$\ge$$ ≥  1% threshold for PD-L1+). We genotyped KRAS and EGFR. Follow-up extended from 120 days post-diagnosis to death, emigration, or 31/12/2014. We computed median survival using Kaplan–Meier methods, and hazard ratios (HRs) using Cox regression associating the biomarkers with death, adjusting for confounders. Among 305 patients, 48% had adenocarcinoma; 38% squamous cell carcinoma. Forty-nine percent had PD-L1+ tumors—51% stage IIIA and 26% KRASm. Few (2%) patients had EGFRm. Median survival in months was 14.7 (95% CI = 11.8–17.9) and 13.4 (95% CI = 9.5–16.3) in PD-L1+ and PD-L1− tumors, respectively. KRASm was not associated with death (HR = 1.06, 95% CI = 0.74–1.51 versus wildtype). PD-L1+ tumors yielded a HR = 0.83 (95% CI = 0.63–1.10); PD-L1+ ICs a HR = 0.51 (95% CI = 0.39–0.68). Tumor expression of PD-L1 did not influence survival. PD-L1+ ICs may confer survival benefit in stage III unresected NSCLC patients.


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