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April turned out to be an exciting month for lung cancer science. First, we attended the 2025 Small Cell Lung Cancer (SCLC) Hot Topic Meeting held in New York from April 2-4, then the American Association for Cancer Research (AACR) Annual Meeting in Chicago from April 24-30. Keep an eye out for our upcoming blog on the AACR meeting.
The SCLC Hot Topic Meeting, hosted by the International Association for the Study of Lung Cancer, has become one of my favorite science meetings. Held at the Memorial Sloan Kettering Cancer Center in New York, the meeting is one of a kind. It brings together scientists conducting preclinical research, doctors who see patients and conduct clinical trials, and other types of scientists such as pathologists and bioinformaticians—all united by the common goal of improving the lives of people diagnosed with SCLC and other neuroendocrine tumors.
A neuroendocrine tumor (NET) is a type of cancer that grows from neuroendocrine cells found in different parts of the body. SCLC is a type of neuroendocrine tumor. Some neuroendocrine tumors are very aggressive, like SCLC, whereas some tend to grow slowly (for example, low-grade NETs).
SCLC comprises 15% of all diagnosed cases of lung cancer. It is considered limited stage (LS-SCLC) when the tumor is restricted to one lung and can be treated with radiation. Once SCLC has spread to the other lung or to other parts of the body, it is called extensive stage (ES-SCLC). Initial treatments for LS-SCLC and ES-SCLC usually involve chemotherapy and immunotherapy.
ES-SCLC tumors often shrink in response to treatment; however, they inevitably find ways to overcome the treatment and grow again. Researchers are working hard to understand why this happens so we can develop better treatments for patients in the clinic. This partnership between laboratory research and clinical science is vital to bringing effective treatments to patients quickly. This year’s SCLC Hot Topic Meeting is a testament to how these collaborations are happening in real-time to improve outcomes of people diagnosed with SCLC.
There were many exciting research projects discussed at the 2025 SCLC Hot Topic Meeting. Here are my top five takeaways.
- Small cell lung cancers are “heterogeneous” and “plastic”
What does this mean? It is now known that SCLC is not just one type of tumor cell but can be different subtypes. The best-known subtypes—which may respond to treatment differently—are:
- SCLC-A
- SCLC-N
- SCLC-P
- SCLC-I
For example, the SCLC-I subtype responds best to chemotherapy-immunotherapy given as the first treatment for ES-SCLC. Even within a single tumor from a patient, the tumor cells may not have just one subtype. In fact, one SCLC tumor can be made up of multiple subtypes of SCLC cells, and therefore SCLC is called mixed or heterogeneous. Data presented at the meeting also showed that subtypes SCLC-A, SCLC-N, and SCLC-P can switch from one cell type to another. For example, SCLC-A cells can become SCLC-P cells—hence they are called plastic.
Why this matters! Understanding that SCLC tumors are mixed and that the cells can switch subtypes is a big step toward developing effective treatments. This research will help scientists develop drugs that target multiple cell types in the tumor.
- Our knowledge of SCLC subtypes is moving to the clinic quickly
What does this mean? In the previous takeaway, I talked about the different subtypes of SCLC. Doctors have already developed a clinical trial to use SCLC subtypes to personalize treatment plans. The phase 2 randomized clinical trial called SWOG S2409 (PRISM) will first test a patient’s SCLC tumor to find out what subtype of cells the tumor has. Then, the doctor will match the patient to the best treatment for that subtype of SCLC.
For example, patients currently living with ES-SCLC receive chemotherapy-immunotherapy followed by immunotherapy maintenance. Based on the results of subtyping, patients enrolled in the clinical trial will receive an additional treatment along with immunotherapy during maintenance. For instance, patients with SCLC-I will receive immunotherapy + monalizumab maintenance therapy. Monalizumab is a type of immunotherapy that activates immune cells such as natural killer cells and T cells.
Why this matters! Researchers have made great progress in developing personalized treatments for non-small cell lung cancer, while personalized medicine for SCLC has been challenging. This trial is a huge milestone that proves personalized medicine is not a dream for SCLC.
- Preclinical research is shedding light on how SCLC becomes resistant to treatment
What does this mean? Preclinical research is also helping us understand how SCLC cells become resistant to chemotherapy and immunotherapy. We know that SCLC cells adapt to chemotherapy by increasing their ability to repair damaged DNA. This allows the cells to survive chemotherapy. Similarly, SCLC also makes less MHC-I protein, allowing the tumor cells to avoid being “seen” by the immune system and survive.
Why this matters! Now that we know how these tumor cells are adapting to survive chemotherapy and immunotherapy, we can develop new, innovative ways to outsmart the tumor cells and eliminate them.
- Preclinical research from the lab is leading to new treatment approaches
What does this mean? There is tremendous momentum in lung cancer research right now—with major findings being presented regularly at scientific conferences. Given the fast pace at which research is moving, doctors have already started using knowledge based on laboratory experiments to develop clinical trials that test new treatment approaches.
For example, iadademstat, a drug targeting the LSD1 protein, is being tested in combination with immunotherapy maintenance as first-line treatment for ES-SCLC. Thanks to preclinical research, we are also seeing more treatments such as antibody-drug conjugates (ADCs) targeting cell surface molecules such as B7-H3 and SEZ6 and bispecific antibodies (BiTEs) targeting cell surface proteins such as DLL3 already in the clinic.
Why this matters! It is important to continue to invest in preclinical research so that we can develop better treatments for patients.
- We’re finally making big improvements in how we treat SCLC
What does this mean? We are seeing big changes in the way we treat both LS-SCLC and ES-SCLC. The recent full approval of tarlatamab (a DLL3-targeting T-cell engager) for ES-SCLC that has stopped responding to initial treatment and the successful ADRIATIC trial that showed the benefit of adding immunotherapy to chemoradiation as initial treatment for LS-SCLC are great examples of how science is helping us to improve the standard of care for treating SCLC.
Why this matters! Let’s take the ADRIATIC trial for example. Patients who received chemoradiation + immunotherapy on the ADRIATIC trial lived 2 years longer (on average) than those who did not receive immunotherapy. This striking difference confirms that research is saving lives. These new treatment innovations are effective, and they are changing the standard of care for patients.
Of course, an important component of all in-person meetings is spending time with leaders in the lung cancer field—such as Misty Shields, MD, PhD. Dr. Shields is a physician-scientist with a special interest in SCLC. She runs a research laboratory, sees patients in her clinic, and also conducts clinical trials.
She is the founder of the Facebook group Small Cell SMASHERS, an online community dedicated to empowering and educating patients diagnosed with SCLC and other NETs. You can see all upcoming LUNGevity events and webinars on our calendar, which includes monthly Small Cell SMASHERS Fireside Chats with Dr. Shields.
LUNGevity is proud to be the largest nonprofit funder of lung cancer research. The progress in treating SCLC is a direct result of research support from nonprofits and, of course, federal agencies. We are deeply grateful to the National Cancer Institute for investing in SCLC research through the Recalcitrant Cancer Research Act of 2013. The investment by the NCI and the work of an international community of patients and their families along with scientists and doctors have made the progress we are seeing today possible.
Join me for my next blog after the Annual American Association for Cancer Research (AACR) Meeting. See you soon!
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