Combination therapy may provide key to treating 85% of lung cancers
Kathryn E. Vinson, MS, CCRC
Non Small Cell Lung Cancer – A little while back, in Cancer Risk to our Veterans, I mentioned my grandfather succumbed to lung cancer after many years of smoking – smoking that began during his service in WWII and persisted for almost the rest of his life. It seems like almost all of us have known someone who has battled or is currently fighting this disease. Nowadays, we learn from a very young age of the dangers of smoking, and the associated risk of lung cancer. There are, however, some other risk factors out there that aren’t as well known, and some promising new treatments on the horizon.
Types of lung cancer
Non-small cell lung cancers (NSCLC) represent anywhere from 80-85% of all lung cancers. These types of cancers affect both smokers and non-smokers. Small cell lung cancers, on the other hand, strike almost only smokers, and tend to spread quickly. Although 80% of cancer deaths are attributable to smoking, the remaining 20% may be linked to radon exposure, second hand smoke, pollution, work-place exposures, or even genetics. Several of these risk factors we can work to avoid or eliminate, such as smoking, but others such as radon exposure, are very difficult to avoid due to its natural occurrence. Researchers are currently looking at cancer and other risks associated with “vaping”, a topic we will talk about more later this week.
For about the last 15 years, scientists have been looking at the epidermal growth factor receptor (EGFR) and its role in the development and treatment of NSCLC. Normally, EGF and its receptors play a role in the healing of wounds, which makes sense when we breakdown the term – epidermal referring to the outer layer of our skin, and growth factor telling us that the chemical is involved in growth and healing. However, it has been shown that EGF and EGFR play also play a role in the development of certain cancers. They found that by inhibiting this receptor, they were able to treat the cancer, but this treatment had a very limited time that it worked, in addition to some pretty nasty side effects.
Unfortunately for patients – cancer is smart – it often finds pathways around treatments. This is precisely what was happening with the EGFR inhibitors. Another factor, called tumor necrosis factor (TNF) was found to increase in NSCLC patients after being treated with EGFR inhibitors, so it stood to reason that this could be the pathway the cancer was using to bypass the treatment. Animal studies showed that tumors were more susceptible to the EGFR inhibitors when that treatment was given in conjunction with a TNF inhibitor.
In the above photo, courtesy of UT Southwestern, we see four rows of tumors. The top row shows tumors that have not been treated, the middle two rows are tumors that have had single therapies, and the bottom row are tumors that received the combination therapy. We can clearly see the difference in size and color of the tumors, and understand the promise that these treatments might hold!
The TNF inhibitor utilized in these animal studies was thalidomide. Yes, the drug that was used by some women in the 1960s to combat morning sickness, that also produced some terrible birth defects. While you may think that it was taken off the market, you’d be wrong. Thalidomide is used also used in conjunction with dexamethasone to treat multiple myeloma; however, it has some very strong restrictions on its use due to its toxicity to developing babies. Interestingly, thalidomide is getting a lot of attention in clinical trials for cancer therapies.
Getting back to the promising treatment for lung cancer, researchers are hoping to be able to fast track the clinical trials involving this combination due to the fact that both drugs already have FDA approvals. The proposed phase II trial is hoped to enroll both patients with NSCLCs and glioblastomas, as EGFR also plays a roll in its development.