The scientific community has made enormous strides in the treatment of lung cancer over the past decade. Armed with knowledge about the specific molecular alterations that drive the growth of lung cancer, investigators have developed targeted therapies that are less toxic to patients and more effective at halting the growth of the tumor. Despite this progress, however, unfortunately lung cancers more often than not develop mechanisms by which they circumvent the effects of even our best drugs. As a result, while many patients initially experience a dramatic response to treatment, the majority suffer from recurrence of disease.
My team and I want to forestall this current reality. To do so, we must gain a better understanding of the reasons why lung cancer cells grow in the presence of certain molecular variations. Specifically, we want to uncover the mechanisms underlying oncogene addiction, the processes that make a lung cancer cell dependent on the activity of a mutant gene in the tumor. The discoveries that we make in this area will undoubtedly permit us to shed more light on a number of currently unanswered questions, including: How does a tumor shrink when we use inhibitor drugs to block the signals emitted by cancer-fueling mutant genes? What enables tumor cells to eventually escape that inhibition? What molecular events dictate response or resistance to targeted therapies?
We are confident that our responses to these queries will offer us the clues we need to develop polytherapies that target both the genetic mutations that drive lung cancer growth and the compensatory pathways that cancer cells utilize to evade conventional therapies. In proposing this way forward, we are proposing strategies that have been used to effectively treat some infectious diseases such as HIV. As you are probably aware, HIV patients receive a cocktail of drugs that specifically target various components of the HIV virus so that, ultimately, it cannot efficiently evolve to the point of resistance. We are optimistic that this approach can be applied successfully to lung cancer. To this end, my team and I continue to use cutting-edge pharmacological and genetic methods to identify logical companion targets that can be included in future polytherapies that we hope will transform lung cancer into a chronic, and even curable, disease.