All cancers are not created equal.
That is the premise behind a growing body of international research, led in part by City of Hope scientists, that is uncovering how individual tumors’ molecular makeup influences treatment success.
Two patients may have the same type of colon cancer at the same stage, but the genetics of their tumors may be different. By taking a genetic fingerprint of patients’ tumors to see what drives their growth and spread, physicians may be able to predict which medications will work best for each patient — and prescribe customized plans offering a greater chance of success.
Learning more about the mechanisms behind cancer also provides scientists with targets for developing smarter drugs.
At City of Hope, one of the leaders of this personalized medicine movement is Yun Yen, M.D., Ph.D., the Dr. & Mrs. Allen Y. Chao Chair in Developmental Cancer Therapeutics and chair of the Department of Molecular Pharmacology.
Yen and his colleagues are investigating how an enzyme called ribonucleotide reductase (RR) contributes to cancer development and spread.
In a recent study, the team showed that patients with advanced colorectal tumors that expressed high levels of a subunit of RR survived longer and had a better prognosis, for example.
Their analysis of more than 300 tumors from patients at City of Hope and the Second Affiliated Hospital of Zhejiang University in China discovered evidence that tumors expressing more of the substance, called RRM2B, were less likely than other tumors to invade surrounding tissue or metastasize to lymph nodes. The study was published online March 17 in Cancer Research.
“The findings suggest that RRM2B might be a potential prognostic biomarker to predict outcome for colorectal cancers,” Yen said. Eventually, physicians might be able to test a patient’s tumor for RRM2B expression and choose therapy based on the results.
These findings follow closely on another success from the City of Hope-Zhejiang team: They found that levels of another protein, called HMGA2 — short for high mobility group A2 — also corresponded to colorectal cancer patients’ survival.
Each of the findings adds to an international library of tumor characteristics that has been growing for well over a decade.
In colorectal cancer, personalized medicine has reached the clinic through tests for a protein called Kras. Patients with colorectal tumors that contain an abnormal version of Kras respond poorly to a particular class of drugs. About 20 to 50 percent of patients with colorectal cancer have this mutation.
Today, doctors can run a test on tumors to see if they express the mutated form of Kras. If they do, patients receive a different treatment right from the start, avoiding unnecessary side effects and receiving a therapy that is more likely to work.
Scientists offer a similar test for nonsmall cell lung cancer. The test can determine if patients have a particular mutation in a gene that makes their cancer more vulnerable to the drugs gefinitib and erlotinib. (Both this test and the Kras test are available through City of Hope’s Molecular Diagnostic Laboratory.)
One private firm offers a test for nearly two dozen genetic markers that can predict whether breast or colon cancer will return. Physicians are evaluating these tests to see how best to incorporate them into treatment decision-making.
“We are enthusiastic about the potential of different biomarkers to improve therapy,” said Yen. “Not only may they help in terms of making treatment decisions, but they help us understand how cancers work. And that may lead to new therapies, as well.”