CRI Immunologists Are Armed Against Lung Cancer, the Most Common Cancer Worldwide 

A Large Cancer Presence on a Global Scale 

The Cancer Research Institute (CRI) has a singular focus: to create a world immune to cancer through the promise of immunotherapy research. Each cancer is unique and presents its own distinct challenges and vulnerabilities to immunotherapy. However, lung cancer warrants a significant amount of attention because it is the most common cancer globally and the second most prevalent in the U.S. 

On a global scale, there are approximately 2.1 million new lung cancer diagnoses annually, along with an estimated 1.7 million deaths linked to the disease. Domestically, the U.S. will experience about 240,000 diagnoses and 130,000 lung cancer deaths in 2023. Lung cancer kills more patients than several other cancers, such as breast and prostate cancers, combined. 

The most common cause of lung cancer is well-documented: smoking. The smoke produced from cigarettes accounts for about 80% of all known lung cancer diagnoses. As we described in a previous blog, cigarette smoke can cause DNA mutations that makes treating lung cancer more complicated. 

There are two major varieties of lung cancer: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). The latter is much more common, comprising between 85-90% of all known lung cancer cases. Unfortunately, by the time many patients are symptomatic, lung cancer has already advanced to the latter stages. By this time, many forms of treatment are only minimally effective. Thankfully, innovative immunotherapy treatments can help improve and even save the lives of lung cancer patients.  

Immunotherapy’s Impact in the Fight Against Lung Cancer 

In 2015, the U.S. FDA approved the first immunotherapy treatment for lung cancer. Since then, there has been a welcome flurry of approved immunotherapies for lung cancer treatment. Five of these treatments are targeted antibodies that alert the immune system to target and destroy dangerous cancer cells. Eight immunotherapy treatments are checkpoint inhibitors, which lift the ‘brakes’ that can sometimes inhibit the immune system from attacking tumor cells. Checkpoint inhibitors are the most well-known and the most effective type of immunomodulator – molecules that operate on the immune system’s pathways. 

These checkpoint inhibitors have been particularly instrumental for improving outcomes for lung cancer patients – even with late-stage cases. There are currently a variety of clinical trials operated by prestigious immunologists who are taking the fight to lung cancer by developing more U.S FDA-approved immunotherapy treatments. 

“We certainly need molecularly driven approaches where we capture immunotherapy response. There are limitations to (current) biomarkers, so there is an unmet clinical need to create dynamic biomarkers that can tell us in real time, and better than with imaging, if patients are responding to cancer immunotherapy,” says Torrey Coast Foundation GEMINI Clinical Accelerator Investigator Valsamo Anagnostou, MD, PhD (Johns Hopkins University). She is heading a CRI-funded NSCLC ctDNA (cell-free DNA in the blood of cancer patients obtained from tumor cells) trial. Dr. Anagnostou’s study is attempting to answer a key question in lung cancer immunotherapy: which patients with metastatic NSCLC can be treated by immunotherapy alone versus immunotherapy and chemotherapy? She continues stating different clinical outcomes depend on different ctDNA responses. “The trial was successful (in the first stage). Now we can reliably and rapidly identify patients who do not attain benefit (from immunotherapy) and intervene. This was crucial to be able to design the second stage of the trial, the ctDNA interventional stage. Our study has opened a therapeutic window of opportunity for the patients who are not likely to attain benefit from immunotherapy alone.”  

Thomas Marron, MD, PhD (Mount Sinai) is a CRI Clinical Innovator whose research focuses on NSCLC. Dr. Marron is also the  director of early phase trials unit and associate director of the Cancer Clinical Trials Office at the Tisch Cancer Center at the Icahn School of Medicine at Mount Sinai. Previously, Dr. Marron found that IL-4, a cytokine usually associated with allergic disease, is produced in lung tumor lesions, and controls the development and variance of myeloid cells in bone marrow and lung lesions.  

“We are curing what was previously incurable lung cancer but only in 15-20% of patients using immunotherapy. We still have a lot of room to grow, and we have a lot of work to do in the clinical trials, and in the preclinical research that we are doing,” says Dr. Marron. 

Since its inception 70 years ago, CRI has provided grants to immunologists striving to make progress in the fight against lung cancer. In 2011, Lloyd J. Old, MD, CRI’s founding scientific and medical director and the father of modern tumor immunology, co-authored a study detailing how lung cancer patients responded to a vaccine targeting the NY-ESO-1 antigen, developed through the CRI/Ludwig Cancer Antigen Discovery Collaborative. By 2018, several CRI Scientific Advisory Committee members and CRI-funded scientists highlighted the benefits of anti-PD-1 checkpoint immunotherapy prior to surgery in patients with advanced lung cancer. 

Those scientists include: 

• CRI Scientific Advisory Council Associate Director Jedd Wolchok, MD, PhD (Weill Cornell Medicine) 
• CRI Scientific Advisory Council member Drew Pardoll, MD, PhD (Johns Hopkins University) 
• CRI Lloyd J. Old STAR Kellie Smith, PhD (Johns Hopkins University) 
• Torrey Coast Foundation GEMINI CLIP Investigator Valsamo Anagnostou, PhD (Johns Hopkins University) 

Despite lung cancer’s prevalence, CRI scientists are striving to curtail its reach and lethality. With their efforts and your support, we can continue making significant strides in immunotherapy and create a world immune to cancer.  

Do you want to do something big for lung cancer? Make a donation to the Cancer Research Institute today.