Kras mutations and resistance to anti-egfr treatment

The disclosure relates to methods of predicting if a subject being treated for colorectal cancer (CRC) with anti-EGFR therapy will develop drug resistance. One method comprises obtaining a biological sample from the subject, assaying the sample for an alteration in KRAS expression, wherein if there is an alteration in KRAS expression, the subject is more likely to develop drug resistance to anti-EGFR therapy. The alteration in KRAS expression may be the expression of a KRAS mutant (somatic mutation), increased KRAS gene or protein expression (focal amplification) or increased KRAS activation, when compared to a control (non-cancerous) sample. Embodiments of the KRAS mutation include G13D, G12R, Q61H or A146T mutation as non-limiting examples. The anti-EGFR therapy may be treatment with cetuximab or panitumumab or other antibody-based therapies as non-limiting examples. The biological sample may be blood, plasma, serum, urine, tissue, cells or a biopsy as non-limiting examples. The present disclosure also provides methods of preventing, reducing or delaying the onset of drug resistance to anti-EGFR therapy as described herein. One method comprises administering, to a subject having an alteration in KRAS expression, an MEK inhibitor in combination with the anti-EGFR therapy. In some embodiments, the subject is afflicted with, or been diagnosed with, colorectal cancer. The alteration in KRAS expression may be the expression of a KRAS mutant, increased KRAS gene or protein expression, or increased KRAS activation as disclosed herein. Non-limiting examples of an MEK inhibitor include XL 518, CI-I040, PD035901, GSK1120212 or selumetinib. The anti-EGFR therapy may be treatment with cetuximab or panitumumab or other antibody-based therapies as non-limiting examples. The biological sample may be blood, plasma, serum, urine, tissue, cells or a biopsy as non-limiting examples. The patent and scientific literature referred to herein establishes the knowledge that is available to those with skill in the art. Genbank and NCBI submissions indicated by accession number cited herein are hereby incorporated by reference. While this disclosure has been particularly shown and described with references to preferred embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the scope of the disclosure encompassed by the appended claims.