Just as physicians have begun looking at breast cancer, lymphoma and leukemia as many different diseases, they are now categorizing lung cancers based on genetic mutations in the tumor cells, says Dr. Nagla F. Abdel Karim , a lung cancer researcher and oncologist at The Ohio State University Comprehensive Cancer Center- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC-James).
For example, non-small cell lung cancer accounts for about 85 percent of all lung cancers, and includes the subset lung cancers of adenocarcinoma, squamous cell carcinoma and large-cell carcinoma.
Karim says that patients who have adenocarcinoma with KRAS gene mutations typically have a worse prognosis than those with that type of lung cancer and with either mutations with the epidermal growth factor (EGFR), no gene mutations or with mutations in a gene called ALK. Patients with ALK translocations, on the other hand, show tremendous response rates to certain molecular targeted therapies that shrink lung tumors.
ALK or anaplastic lymphoma kinase, was discovered several decades ago as an enzyme found to be abnormally regulated in certain types of lymphoma. Only three years ago, researchers discovered that ALK can also be abnormally regulated in certain types of lung cancer.
“Personalized treatments are beginning to make a real difference,” Karim says. “For example, early studies suggest that treating patients with ALK translocations with an ALK specific inhibitor rather than chemotherapy may be much more effective and less toxic. Ongoing studies will test whether this initial impression is true. This would be a huge difference that we can’t ignore.”
More research is needed to find new drugs to target these and other genetic mutations in lung cancers, she says.
“As recently as 10 years ago, everyone thought that it’s only one type of disease, and everybody responds the same way,” says Karim. “Now we are personalizing the treatment, based on the patients’ molecular profiles and the histology of their tumor cells, which is improving treatment outcomes.”
For example, researchers at OSUCCC-James are conducting a Phase II clinical trial for patients with advanced non-small cell lung cancer that combines standard treatment of carboplatin chemotherapy with nanoparticle albumin bound paclitaxel (nab-paclitaxel), a drug that has received by the U.S. Food and Drug Administration to treat patients with metastatic breast cancer. Nab-paclitaxel has shown improved response rates in breast cancer patients (compared with the non-nanoparticle form of paclitaxel), and researchers are hoping it will do the same for lung cancer patients.
“Even after 30 years of improving therapeutic approaches, the 5-year mortality rate of lung cancer remains an alarmingly high 86 percent,” says Karim.
Lung cancer is the leading cause of cancer death in the United States and worldwide. There are more deaths annually in the United States from lung cancer than colorectal, breast and prostate cancer combined. More than 220,000 new cases of the disease are expected this year, along with almost 160,000 deaths, according to the American Cancer Society.
“Although lung cancer is the number one cancer killer, it has much less funding for research. Unfortunately, patients are often blamed for being smokers, and that’s why they got it. However, people 60 years ago didn’t know that smoking was something bad,” says Karim.
Each year, more than 20,000 lung cancer deaths occur among men and women who are lifelong nonsmokers. During the past decade, researchers have begun studying the subtle differences found in the tumors of smokers and those who have never smoked.
“About 85 percent of people who develop lung cancer are smokers, and there is an urgent need to continue additional research on smoking-related lung cancer and ‘personalizing’ therapy for this group of patients,” says Dr. Gregory Otterson, co-director of the thoracic oncology program at OSUCCC-James.
Symptoms of lung cancer often don’t appear until the disease is advanced, and there is still no easy way to diagnose the disease. Symptoms may include persistent coughing or wheezing, chest pain, shortness of breath, coughing up blood or unexplained weight loss. Early detection is often difficult because there are no standard screenings available, says Karim.
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (cancer.osu.edu) is one of only 40 Comprehensive Cancer Centers in the United States designated by the National Cancer Institute. Ranked by U.S. News & World Report among the top cancer hospitals in the nation, The James is the 180-bed adult patient-care component of the cancer program at The Ohio State University. The OSUCCC-James is one of only seven funded programs in the country approved by the NCI to conduct both Phase I and Phase II clinical trials.
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