Just because a chemotherapeutic drug exist does not mean it will work for every patient. There has been no other time when this sentiment has resonated more soundly than now, in the era of personalized medicine.
In the case of colorectal cancer, a diagnosis isn’t quite enough, as nearly half of the patients are apparently resistant to the drug regimen commonly used as a first-line defense in this cancer. "The challenge is that we do not know beforehand in which 50% the treatment will work. This means we have to treat all patients in the same way - including the 50% who do not benefit, " said Claus Lindbjerg Andersen, professor at the Aarhus University Hospital who led the research efforts to find new biomarkers for colorectal cancer.
Colorectal cancer, also known as colon cancer or bowel cancer, is the third most commonly diagnosed cancer type in the world. The cancer usually begins as small, benign lumps of cells that form polyps in the colon. Without proper removal, these polyps can turn cancerous and cause symptoms such as abdomen pain, rectal bleeding, weakness, and fatigue. According to a recent report, the incidence of colorectal cancer is expected to increase by 60% to more than 2.2?million new cases and 1.1?million deaths by 2030.
The goal was to better predict which set of patients will respond to Oxaliplatin, a chemotherapy drug widely used in colon cancer. By looking at the genetic profile of patients treated with oxaliplatin, the researchers found differences in those who seemed to respond to the drug, versus those who seemed to be resistant to the treatment.
The difference? A microRNA molecule known as miR-635-3p. The presence of this molecule appeared to prevent oxaliplatin from killing the colorectal cancer cells. Thus, those with this biomarker are unlikely to benefit from oxaliplatin. In fact, the team found that,"Patients with tumors positive for the molecule actually have a six times higher risk of being treatment-resistant than other patients,” said Mads Heilskov Rasmussen, first author of the paper.
Current detection methods for colorectal cancer include invasive colonoscopy procedures that check for the presence of pre-cancerous polyps. When polyps are found, physicians can remove it before they turn into cancer. Another source of detection is through screening patients for commonly mutated genes that are associated with colorectal cancer. But detection is nowhere enough if the treatments offered to patients have a high chance of not working.
With the microRNA biomarker, doctors could screen colorectal patients and identify those who may or may not respond to the oxaliplatin ahead of treatment initiation. This would spare patients who express the microRNA biomarker from undergoing fruitless treatments, in favor of those that might have a better chance of being effective.
"Our discovery also opens up for development of new treatment strategies as we have shown that if the microRNA is eliminated from the tumor, the effect of Oxaliplatin is restored" says Claus Lindbjerg Andersen. Accordingly, combination therapies could be a way forward.
Additional source: Aarhus University Hospital