Small Cell Lung Cancer Not A Uniform Disease

Small cell tumors respond differently to treatment.

It is well understood that there is no 1 magic pill to treat all cancers. In a new study published in Cancer Cell, investigators found distinct types of tumors within small cell lung cancer, suggesting this form of cancer should not be treated as a uniform disease.

“Currently, when small cell lung cancer patients come in, there is no genetic testing for them,” said investigator Trudy G. Oliver, PhD. “They’re just diagnosed with small cell and they are all treated basically the same way. But our research showed small cell tumors do not all act alike. That becomes very important in how a patient is treated.”

The investigators used mice to create the first known replica of C-MYC, a small cell tumor subgroup. It’s estimated that this tumor comprises approximately one-fifth of patients with small cell lung cancer.

“The C-MYC tumors physically look different under the microscope,” Oliver said. “They’re much more aggressive. They grow faster and they spread faster. And most importantly, they respond differently to therapy.”

Small cell lung cancer accounts for approximately 30,000 deaths in the United States per year. Traditionally, the disease is treated with chemotherapy; and although it demonstrates efficacy in approximately 80% of patients, the tumors can quickly develop chemo-resistance.

According to the authors, a majority of drugs tested have been unsuccessful, but they had not been tested on a live C-MYC model.

Through a collaborative effort, the investigators analyzed the properties of the C-MYC tumor, and sought to identify drugs that could work with this type of small cell tumor. They found that Aurora kinase inhibitor plus chemotherapy improved outcomes for the mice.

“The mice survived about twice as long,” Oliver said. “We have some mice that really had extended survival. If these observations could be translated to people, this could be a significant breakthrough for patients with small cell lung cancer.

“Historically, when you would test a drug in small cell lung cancer, almost everything failed. You’d maybe have 10% or 20% of people respond—–and you didn’t know why those did. So now that we have a new appreciation for the different molecular types of tumors, we might realize, ‘Oh, 100% of this tumor subgroup actually responded––it just happened to be only 20% of the whole.’”

The findings suggest the importance of genetic testing for small cell lung cancer, according to the authors.

“We should be able to do molecular testing to say, ‘You have this type of small cell versus this type,’” Oliver said. “That really matters because it’s going to dictate which therapy you should get. We also need to find therapies that work specifically for each type of tumor.”

The investigators noted that the study results could impact other neuroendocrine tumors, such as brain, gastrointestinal, pancreatic, or prostate cancers.