A promising personalized approach to treat small cell lung cancer
Small cell lung cancer (SCLC), which accounts for 10-15 percent of all lung cancer cases, is extremely aggressive, with a five-year survival rate of about two percent. Although SCLC can arise from a diverse range of genetic mutations—meaning each patient’s tumor is unique—all patients are treated the same way, with platinum-based chemotherapy.
A new study that includes contributions from Robert Wechsler-Reya, Ph.D., professor at SBP, makes an important advance toward a better, more precise therapy for patients whose tumors share a key genetic alteration—extra copies of a gene called MYC. The research, published in the journal Cancer Cell, suggests that combining Aurora kinase inhibitors, a relatively new class of anti-cancer drugs, with chemotherapy may improve outcomes for patients with MYC-driven tumors.
The research comes from the lab of Trudy Oliver, Ph.D., an assistant professor at the Huntsman Cancer Institute at the University of Utah (and a former graduate student of Wechsler-Reya’s). With the help of mice generated by Wechsler-Reya’s lab, Oliver created a new model of MYC-driven SCLC, and used it to demonstrate that the combination of Aurora kinase inhibitors and chemotherapy was more effective in slowing tumor progression than either drug alone.
“The new findings suggest that this drug combination may be effective in patients with this devastating form of lung cancer, which accounts for 20 percent of small cell cases,” says Wechsler-Reya. “And since several Aurora inhibitors are already in clinical trials for other cancers, trials in SCLC patients could start soon.”
The research builds on prior results from another collaborator on the paper, Martin Sos, Ph.D., junior research group leader at the University of Cologne, whose in vitro studies found that SCLC cell lines with extra MYC are susceptible to Aurora kinase inhibitors. The new study looked at whether that’s also true of MYC-driven tumors in vivo, using the new mouse model that was created with the help of Wechsler-Reya’s lab.
The research also establishes the relevance of the mouse model by showing that MYC-driven SCLC, as suggested by studies in patients, is particularly bad—it grows and metastasizes very rapidly. Just as importantly, they found that this subtype is distinguishable by its appearance and by a combination of markers, which could help identify which patients will benefit from Aurora inhibitors.
“Clinical trials of Aurora kinase inhibitors alone have yielded mixed results in SCLC patients,” adds Oliver. “Our findings suggest that those drugs may work better if they’re combined with chemo and given only to patients whose tumor morphology and markers indicate they’re driven by MYC.”
The paper is available online here.
Hear Wechsler-Reya discuss his lab's contribution: