An understanding of what the different KRAS mutations are in NSCLC and how they modulate the efficacy of cetuximab could perhaps reveal similar subsets of KRAS mutations with specific predictive value to treatment options of NSCLC.
The impact of RAS mutations in KRAS exon 3 and 4 and NRAS exons 2, 3 and 4 appears to be similar to that of KRAS exon 2 mutations, with all mutations being predictive of a lack of response to panitumumab therapy.
In addition, several biomarkers have been proposed in association with KRAS mutations as predictive markers for the efficacy of the anti-EGFR moAbs including BRAF [19], [22] or PIK3CA mutations [21], EGFR ligands overexpression [23], [27], PTEN protein expression [28] and EGFR copy numbers [10], [11].
While predictive power increases when more mutations with smaller effects contribute, predictability is retained down to relatively small number of mutations contributing to fitness differentials.
For the oncogenic detection application, it has been introduced into the clinical analysis and was further designed as streamlined commercial products with targeted panels which cover the main genetic alterations with predictive value, including EGFR mutations [ 61, 63– 63].
116 Recent advances in technology have shed more light on the complexity of breast cancer biology and have provided data that allow risk estimation for patients with inherited mutations, prognostic and predictive determinations for patients with sporadic breast cancer, and targets for therapies.
It is not possible, however, to analyse the predictive value of mutations with respect to EGFR-blocking therapy in our patient cohorts due to the lack of such treatment during the cohort recruitment.
The good predictive value of EGFR mutations and poor predictive value of KRAS mutations with regard to EGFR TKI treatment was not reflected in terms of prognosis in our patient cohort.
Activating EGFR mutations are predictive of response to EGFR inhibitors with reported response rates of upto 75%.
KRAS mutations are predictive markers for the efficacy of anti-EGFR antibody therapies in patients with metastatic colorectal cancer.
