Colorectal Cancer (CRC) is now the third leading cause of cancer-related deaths in the U.S. A report in Foundation Medicine highlights data on the increase in the number of cases among people under the age of fifty. The American Cancer Society reports that half of the new rectal and colon cancers occur in people younger than sixty-six.
These very significant statistics have caused clinicians to delve deeper into locating the cancers’ drivers. Researchers are attempting to identify how they differ across age groups and how their findings can assist in treating cancers.
Considering Comprehensive Genomic Profiling
In the realm of driver mutations, KRAS mutations represent approximately thirty to fifty percent of the drivers in colorectal tumors.
Although the KRAS can be helpful in understanding the tumor growth and predict progression, patients with the KRAS mutation may not respond well to the anti-EGFR (estimated glomerular filtration rate).
In this regard, efforts are now underway to locate relevant biomarkers that would determine treatment recommendations.
Researchers conducted a prior study of four thousand CRCs. They looked at recurrent mutations that could provide clues to either a response or resistance to targeted therapies.
Their study shows the importance of submitting tumor samples for testing through genomic profiling rather than hot spot or testing single genes.
The Significance of Age in CRC
Researchers have learned that CRC’s genomic drivers are influenced by the patient’s age. This is of interest to clinicians due to the recent increase in younger patients with CRC.
Another study by Foundation Medicine showed that two alterations, CTNNB1 and TP53, appeared more frequently in patients under the age of forty.
The same study showed that BRAF, FAM123B, and KRAS were found frequently in patients over the age of forty. The researchers point out the importance of comprehensive genomic profiling to identify potential alterations.
Looking Ahead
In spite of the progress so far in CRC research, there is still a tremendous amount of work ahead to develop treatment options for patients.
Although each patient should be treated as being unique, it is still important to look for commonalities among all age groups in order to determine the best treatment options.
About Microsatellite Instability High
Fifteen percent of CRCs are either microsatellite instability or MSI high. That means that cancer cells with high numbers of mutations within microsatellites are excellent biomarkers and will be recognized by the immune system. That would make the tumors sensitive to checkpoint inhibitor immunotherapy.
But what about the other eighty-five percent of CRC patients who have stable microsatellite disease? How do we locate the remaining responders? TMB may provide the solution.
About (TMB) the Tumor Mutational Burden
The biomarker TMB has shown efficacy in predicting immunotherapy response in many different types of cancer. It may work with MSI to determine potential responders.
Researchers and collaborators at Foundation Medicine published the largest TMB study to date. They determined that TMB may be able to identify almost all patients with MSI-high as well as patients with microsatellite stable CRC. Immunotherapy may therefore be of benefit in these cases.
Foundation Medicine Inc. will continue its efforts to locate other relevant biomarkers as options for treatment decisions.
