Using next-generation sequencing technology, researchers have identified multiple gene mutations that may alter a patient's response to panitumumab for metastatic colorectal cancer, according to results of a study presented at the American Association for Cancer Research 101st Annual Meeting 2010.

"One of the pressing goals is to identify predictive biomarkers for drugs such as panitumumab. This technique provides a method to simultaneously evaluate multiple genes within a tumour," said Dr. David M. Reese, Executive Medical Director in medical sciences and head of the oncology early development group at Amgen, Thousand Oaks, California.

Reese and colleagues used the Roche 454 pyrosequencing technology to investigate whether mutation of genes, beyond the KRAS gene mutation, altered colorectal cancer response to panitumumab. KRAS gene mutation is an established biomarker for a lack of response to anti-epidermal growth factor receptor antibodies. Using tumour samples from 288 patients with metastatic colon cancer, they investigated mutations in nine genes: KRAS (exon 3), BRAF, NRAS, AKT1, CTNNB1, EGFR, PIK3CA, PTEN and TP53.

On average, eight genes were evaluable per patient. More than one mutation was found in 109 tumours and 20 tumours had more than one mutation in a single gene. Two tumour samples yielded KRAS and BRAF mutations, suggesting that the presence of these mutations together is not always mutually exclusive, which has been previously reported, according to Reese.

Further, this study confirmed that simultaneously testing multiple biomarkers in one tumour sample is possible.

"The ability of this sequencing technology to assess multiple genes in parallel may permit the more rapid development of truly personalised medicine," said Reese.

There is still much work to be done though, according to the researchers. Two large Phase III trials have been completed and the next step is to see if the predicative ability of these genetic profiles is influenced when patients undergo combination chemotherapy.

Source: The American Association for Cancer Research