Patterns of gene copy number aberrations (CNAs) in isolated small-cell lung cancer (SCLC) cells may help determine how patients will respond to chemotherapy, according to a study published in Nature.
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SCLC is often difficult to treat and the leading cause of cancer death. But researchers have discovered that a simple blood test, which detects patterns of CNAs in isolated cancer cells, can predict whether patients with SCLC will respond to chemotherapy treatment.
Researchers, led by Caroline Dive, PhD, Clinical and Experimental Pharmacology Group at the University of Manchester (UK), conducted a study that examined CNAs in circulating tumor cells (CTCs) from pretreatment SCLC blood samples of 13 patients. The purpose of the study was to differentiate genetic features that distinguish chemosensitive from chemorefractory disease, or relapse that occurs within three months of initial treatment.
After 88 isolated CTCs from 13 patients were analyzed, researchers generated a CNA-based classification system that was validated in 18 additional patients (112 CTC samples) and in 6 SCLC patient-derived CTC explant tumors. The classification system correctly assigned 83.3% of the isolated cases as either chemosensitive or chemorefractory. By using the classification system, there was also a significant difference in progression-free survival between patients classified as chemosensitive or chemorefractory (P = .0166).
Five patients with chemosensitive disease who relapsed had their CTC CNA profiles recorded at relapse. These patients did not switch to a chemorefractory CNA profile, indicating that the genetic basis for initial chemoresistance differs from that underlying acquired chemoresistance and that different mechanisms of drug resistance developed in these patients.
"By identifying differences in the patterns of genetic faults between patients, we now have a starting point to begin to understand more about how drug resistance develops in patients with this aggressive form of lung cancer," explains Dr Dive.
