While more effective chemotherapy agents have improved cancer survival, not all patients benefit from the drugs.
Now, a team of researchers from Academia Sinica and the National Taiwan University College of Medicine say they have identified an eight gene “signature” that predicts how long cancer patients might survive without relapse after undergoing chemotherapy.
Predicting how well patients respond to chemotherapy drugs, the toxic agents that can decimate not just tumor cells but healthy ones as well, involves a complicated calculation of how active tumor genes are, how likely cancer cells are to spread to other sites, and how effective the chemotherapy drugs are in targeting and destroying abnormally growing cells. To find the genetic markers in cancer cells that might provide clues to their response to chemotherapy, the researchers relied upon the the National Cancer Institute’s panel of 60 human cancer cell lines, known as NCI-60, which represent leukemia, melanoma, lung, colon, ovarian, renal, breast and prostate cancers, among others. From this panel, they identified 633 genes that were associated with a cancer cell’s ability to spread, or invade other healthy tissues. They then compared how these genes reacted to 99 different anti-cancer drugs and found eight genes that showed a strong correlation to an elevated response to five chemotherapy agents — dasatinib, docetaxel, erlotinib, everolimus and paclitaxel.
The eight genes seemed to provide patients with a better chance of responding to chemotherapy, but to confirm the link, the researchers also turned to published studies of cancer patients to see if their panel could predict longer survival. And indeed, lung and breast cancer patients in these trials with the eight gene signature showed a lower risk of recurrence and longer relapse-free survival than patients without the genetic markers.
Study author Ker-Chau Li, a professor from Academia Sinica and University of California Los Angeles explained in a statement:
Our study found eight genes which were involved in invasion, and the relative activation of these genes correlated to chemotherapy outcome, including the receptor for growth factor EGF. We also found that some invasion genes had unique patterns of expression that reflect the differential cell responses to each of the chemotherapy agents – [and] five drugs (paclitaxel, docetaxel, erlotinib, everolimus and dasatinib) had the greatest effect.
According to Li’s team, identifying such biomarkers for cancer patients can lead to more personalized, and potentially more effective chemotherapy treatments. Understanding the genetic makeup of individual patients’ tumors can provide hints as to which chemotherapy agents are most likely to compromise or shrink those tumors, and lower risk of relapse.
They note, however, that cell lines may react differently than cancer cells in the body, but are encouraged that finding such genetic profiles or markers could lead to more refined and effective treatments. Chemotherapy agents are becoming more targeted, designed to find cancer cells and leave healthy ones alone, but combining such advances with more precise matching of tumors to the chemotherapy drugs that work best to destroy them could lead to even longer, and more sustained survival for more cancer patients.
The study is published in the journal BMC Medicine.