Ramesh Ganju, PhD

American Lung Association Lung Cancer Scholar

About 85% to 90% of lung cancers are non-small cell lung cancer (NSCLC). Many patients with the disease become resistant to chemotherapy, and fewer than 20% of patients live beyond five years after diagnosis. Dr. Ganju is using an American Lung Association Lung Cancer Discovery Award to investigate potential novel treatments to extend the lives of patients with NSCLC. He is focusing on receptors called CB1 and CB2 found on cells that regulate the progression and spread of NSCLC to other organs and systems. Natural brain compounds called endocannabinoids, which are similar to THC—the active ingredient in marijuana—bind to CB1 and CB2. Dr. Ganju will test these compounds’ effect on the growth and spread of lung cancer in a mouse model that is genetically engineered to develop lung cancer. “We believe endocannabinoids inhibit tumor growth, but this action is blocked by an enzyme called fatty-acid amide hydrolase (FAAH), which degrades, or breaks down, endocannabinoids,” Dr. Ganju says.

“This research will hopefully lead to much needed treatments for NSCLC and could not have been possible without the support of the American Lung Association.”
His first goal is to find out whether FAAH is being produced in lung cancer tumor samples. If this is the case, he will examine whether blocking FAAH might allow endocannabinoids to slow down or stop lung cancer growth. He will treat mice that develop NSCLC with a substance that inhibits FAAH, to find out if this treatment will increase the concentration of endocannabinoids and allow them to block tumor growth. He will also give NSCLC mice a direct treatment with endocannabinoids, to see whether the compounds have an effect on tumor growth and spread.

Finally, he will examine genetically engineered mice that have a mutation that causes them to develop drug-resistant tumors. He will treat these mice with endocannabinoids and FAAH inhibitors to see if one or both treatments can be used successfully against drug-resistant tumors to inhibit lung cancer growth. This research would not have been possible without the American Lung Association grant, Dr. Ganju says. “We had initial data, but we didn’t have money to proceed,” he says. “This grant will help us to establish all of these models that could lead to new treatments for NSCLC. This is especially imperative considering the resistance of this lung cancer to chemotherapy and the poor prognosis of NSCLC patients.”;