A Dose Of Hope: Individualized Treatments Lend Promise To Those Battling Lung Cancer

Feb 7, 2017

Dave Ledbetter and his daughter Rhesa (circa 1985). Dave was recently diagnosed with small cell lung cancer.

“Rhesa, I have cancer,” he said. Although there were indications it could be cancer, I never really thought those words would come out my dad’s mouth. Or maybe I was just living in denial that my dad only 61 years old could actually have cancer. I held back the tears. Many have lived through similar moments—all of us victims in some form or another of the terrible “C” word.

My dad was recently diagnosed with small cell lung cancer. He is now part of a statistic, 1 of about 30,000 people affected each year in the United States. I wasn’t too surprised the cancer was in his lungs. He used cigarettes for 50 years of his life, and the majority of small cell cases arise in smokers. My dad shared more details saying there’s a golf-ball size mass on his lung, spots on his adrenal glands, and chemotherapy is the treatment. While he chose to move forward with chemo, the decision was difficult. The survival rate for this cancer is poor, many patients not making it past 10 months. As hard as it was to stomach, I wanted to know more.

Within days of my father's diagnosis, an email entitled “Lung Cancer Treatment: Researchers Found More Effective Drug For Aggressive Tumors” arrived in my inbox. (As a science reporter, I often receive news stories). I was shocked when the article specifically addressed small cell, since this type of cancer is only 10-15% of all lung cancer cases in the United States. There were some major breakthroughs taking place—I felt a glimmer of hope.

Dr. Trudy Oliver is unraveling tumor growth in small cell lung cancer and working on new treatment options for patients.
Credit University of Utah

Trudy Oliver, an assistant professor in the Department of Oncological Sciences at the University of Utah and an investigator at Huntsman Cancer Institute, pointed out that small cell lung cancer is now just starting to get the attention it deserves.

“This tumor type has been treated with chemo for about 40 years, the same therapy. Patients respond very well to chemotherapy and often think they are cured. They had disease everywhere, get treated with chemo, and it looks like they are cured. But they are basically never cured. There will still be some residual cells in the body, and those become resistant to the chemotherapy. [The cancer] comes back, and no matter how you treat them they stop responding,” she said. “It mentally plays tricks on people. For 40 years, we had no second-line treatment. Once people become resistant to chemo, we have had nothing to offer them.”

Oliver emphasized that a one-treatments-fits-all approach just doesn’t cut it.

“Our recent work says not all small cell is the same. There are categories of small cell, and we need to tell a patient what type they have, because that will influence what type of therapy they should get,” she said.

For some types of cancer, there is genetic testing. Scientists can take a deep look into the cancer cells’ DNA for example to determine the subtype and then offer the best treatment. This is not yet available for small cell.

“Small cell has been behind,” Oliver said. “In the most common kind of lung cancer called adenocarcinoma, it’s routine that if you came in, we would take DNA and do all types of molecular testing on your tumor. We would stratify you into different categories. That category would impact what type of therapy you got.”

Determining subtypes and understanding the way they behave is critical to developing more effective treatments. Oliver’s work has demonstrated that there are two major subtypes of small cell lung cancer tumors known as L-MYC and C-MYC. Each tumor type displays distinct properties—for instance, C-MYC looks different from L-MYC under a microscope.

While both subtypes have a similar reaction to chemotherapy,—an initial response followed by resistance—Oliver and her team found the C-MYC subtype responds very well to a more specific therapy, a drug called an aurora kinase inhibitor in conjunction with chemotherapy. Mice undergoing the combination therapy lived about twice as long, some even longer. This positive outcome could have huge implications for human patients.

“So, if you came in today and you had the C-MYC subset, we would want to enroll you in a clinical trial for an aurora kinase inhibitor plus chemo,” said Oliver. “But if you had L-MYC, we don’t have a therapy for you beyond chemo. This finding has provoked us to look for drugs that work for the L-MYC subset. We now have some great clues about what drugs work for that subset.”

Oliver hopes that as early as next year doctors will be running genetic tests on small cell tumors to determine the subtype and ultimately the best treatment for a given individual—no more of a one- treatment-fits-all approach, but rather a personalized treatment. While chemo is currently the only approved therapy, new clinical trials are underway.

“We don’t have approved drugs for them yet,” Oliver said, “but that is where the clinical trials should and are going to immediately start to show that these drugs work better in some subtypes. Hopefully not too much further down the road, those drugs will be FDA approved for these subtypes, so when patients are tested they’ll have options.”

During our interview, I found myself overwhelmingly grateful for the work scientists like Dr. Oliver are doing. While my dad and so many others are battling cancer, knowing more effective treatments are making their way to patients is encouraging. My dad just may be at the forefront of big changes in small cell lung cancer diagnosis and treatment. Perhaps a clinical trial is in his near future.  

And Dad—you know I’m rooting for you!

Additional information: Dr. Oliver's recent studies on small cell lung cancer were published in Cancer Cell.