Read time: 4 minutes.
As a dedicated researcher and oncologist, Noura Choudhury, MD, at the University of Chicago, witnesses daily the urgent need for better treatments for lung cancer. She is passionate about finding the most efficient ways to help her patients—particularly those diagnosed with small cell lung cancer (SCLC).
SCLC accounts for about 15% of all lung cancer diagnosis. It is known to be aggressive and difficult to treat and can be associated with high levels of mutational burden from tobacco exposure. Despite significant advances in treating non-small cell lung cancer (NSCLC), progress in treating SCLC has lagged.
“One of the challenges facing researchers is a scarcity of serial SCLC tissue samples,” explains Dr. Choudhury, “because repeating biopsies when the disease progresses is not part of the standard of care for many patients.”
While current options for treating SCLC have expanded to include newer treatment options, such as immune checkpoint inhibitors (ICI) and BiTe technology, the tumors quickly develop resistance to ICI treatment and begin to grow again. Researchers are now exploring new strategies to combat this drug resistance to ICIs.
Orphan Drugs
In 2023, Dr. Choudhury was on the lookout for a treatment for lung cancer—something that could be quickly tested and brought to patients safely and effectively. Her focus turned to orphan drugs—pharmacological compounds with the potential to offer significant benefit for neglected (or “orphaned”) diseases—those affecting fewer than 200,000 people in the U.S.
There are over 100 drug entries listed for the treatment of lung cancer in the orphan drug database. Each of these drugs has been approved for orphan status by showing the drug could have a profound impact on treating a specific type of lung cancer. If additional research emerges adding to the promise of an orphan drug, the NIH may issue a request for applications (RFA) to identify and select researchers interested in testing the drug.
NIH as the Matchmaker
Dr. Choudhury had just started a medical oncology fellowship at Memorial Sloan Kettering Cancer Center (MSKCC) when a research team there, led by Charles Rudin, MD, PhD, deputy director of MSKCC and chair of LUNGevity’s Scientific Advisory Board, made an important discovery.
Their research suggested a protein called lysine-specific demethylase 1 (LSD1)—which is known to regulate the immune system—could be an effective target for overcoming ICI resistance. Mouse models of ICI-resistant SCLC treated with a combination of ICI and iadademstat, an LSD1 inhibitor, showed promising results from the addition of the LSD1 inhibitor. Iadademstat is a small molecule taken by mouth that was granted orphan drug status by the FDA for the treatment of patients with SCLC based on initial safety data.
Shortly after the data was published, the NIH’s Cancer Treatment Evaluation Program (CTEP) released an RFA to find researchers who were ready to study the orphan drug iadademestat in SCLC.
Dr. Choudhury prepared a comprehensive and compelling CTEP application and received a CTEP grant to conduct a phase I/II randomized clinical trial investigating the efficacy of combining iadademstat with ICI for patients living with extensive-stage SCLC.
Hope for Patients
Dr. Choudhury received LUNGevity’s coveted Career Development Award to use novel plasma-based assays to study the evolution and expression of key transcription factors in liquid biopsy samples taken during the clinical trial to study how SCLC evolves during treatment.
In addition to providing reliable research funding, the award also offers tremendous career opportunities to network with giants in the field and to build critical science communication skills.
“I am interested in an academic career where I have protected research time. But that's not something that's handed to you on a silver platter. You have to show that you are capable and deserving of the time to do the science,” said Dr. Choudhury. “Getting an award like this from LUNGevity bolsters your credentials. It means a lot.”
Dr. Choudhury and her team are now recruiting patients for this crucial clinical trial, aiming to make significant strides in understanding drug resistance mechanisms in SCLC and leveraging a promising orphan drug to overcome drug resistance.
Deeper Reading:
- Learn about the $54 million dollars (and counting) invested in LUNGevity’s Research Program: Lung Cancer Research | LUNGevity Foundation
- FAQs About Designating an Orphan Product from FDA
- Explanation of how the NIH is structured to oversee orphan drug testing
- Historical perspective on how orphan drugs got their name
- Important research papers laying the foundation for the role of LSD1 in treating SCLC with immunotherapy
- Targeting LSD1 Rescues MHC Class 1 Antigen Presentation and Promotes Immune Checkpoint Blockade Response in Small Cell Lung Cancer
- Targeting Lysine-Specific Demethylase 1 Rescues Major Histocompatibility Complex Class I Antigen Presentation and Overcomes Programmed Death-Ligand 1 Blockade Resistance in SCLC - Journal of Thoracic Oncology