Multiplicity of EGFR and KRAS mutations in non-small cell lung cancer (NSCLC) patients treated with tyrosine kinase inhibitors.
BACKGROUND
Concurrent presence of EGFR and KRAS mutations in non-small cell lung cancer (NSCLC) patients is relatively rare and their appearance is believed to be mutually exclusive. Tumours harbouring KRAS mutation are perceived as not being capable of response to tyrosine kinase inhibitor (TKI) therapy.


METHODS
This paper presents 5 case reports of patients with tumours harbouring multiple EGFR and/or KRAS mutations. There were 3 patients with EGFR mutations (2 x exon 19 deletions, 1 x L858R) combined with KRAS mutations (2 x Gly12Asp, 1 x Gly12Val), 1 patient with two EGFR mutations (exon 19 deletion + L858R) and 1 patient with two KRAS mutations (Ala11Pro + Gly12Val).


RESULTS
All EGFR(+)/KRAS(+) patients had initially showed positive response to TKI treatment. The EGFR(+)/EGFR(+) patient has exhibited strong rash and good response with the best survival, while the KRAS(+)/KRAS(+) patient did not respond to TKI therapy.


CONCLUSIONS
EGFR(+)/KRAS(+) combination does not necessarily pose a negative prediction. This is probably due to the multiclonal character of the tumour displaying partial response in the EGFR(+) subpopulation.
Benesova
Lucie
L
Laboratory for Molecular Genetics and Oncology, Genomac International, Ltd., Prague, Czech Republic.
Minarik
Marek
M
Jancarikova
Dana
D
Belsanova
Barbora
B
Pesek
Milos
M
D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D011905:Genes, ras; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D009154:Mutation; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D018631:ras Proteins / Q000235:genetics*
D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D018631:ras Proteins