Subtyping in SCLC: Adding More Letters to the Alphabet Soup
June 5, 2026
When we try to characterize small cell lung cancer (SCLC), we typically define it by its stage, either extensive stage or limited stage. We don't often delve further than that; that's about as specific as we'll hear. However, you may be surprised to learn that there are actually 4 unique subtypes of small cell lung cancer, each with its own characteristics. The reason these aren't often discussed, though, is that for a while we weren't certain what this information meant. Yes, there are differences among these 4 types at the cellular level, but what does that really mean for the person living with the disease? In recent years, though, this has begun to change. Scientists have been working to uncover how these small differences can potentially have a great impact on the future of personalized medicine and small cell lung cancer. Here, we'll discuss a little bit about each of these 4 subtypes, and how the treatment landscape may shift to accommodate them in the future.
To differentiate the types of SCLC, we have to look at the different proteins that are inside of the cancer cells. These special proteins can help determine how the genes of the cancer cells express themselves, which in turn can impact how these cells grow, reproduce, and react within the body. By taking a blood sample and looking at the circulating tumor DNA (ctDNA) to examine these factors, doctors and scientists can see what type of subtype a person's SCLC is.
SCLC Subtype-A
These are SCLC type cancers where there is a high expression in the cells of a factor called ASCL1. This is the most common subtype, found in between 40% and50% of cases. Some early research shows that this subtype might be more susceptible to a type of drug called BL-2 inhibitors. These drugs work by blocking a protein inside of the cells that can then cause the cell to die. Some research suggests that this sub-type, after treatment with chemotherapy, may convert to sub-type I (discussed lower down).
SCLC Subtype-N
This subtype means that a person's SCLC cells have a lot of the factor NEUROD1. This factor is important to helping certain specialized cells grow and function within the body, and it is found in high levels in many cases of extensive-stage disease. This subtype is found in about 20% of SCLC cancers. While this subtype can mean the cancer is a bit faster in how it grows and spreads, it is also more sensitive to treatment with a type of drug called Aura-Kinase inhibitors. These are still in trials for SCLC, and we are monitoring the progress of this research for future uses.
SCLC Subtype-P
Having the subtype of SCLC-P indicates that your cancer has higher levels of the POU2F3 factor. This is a factor used by specialized cells that line the respiratory and digestive systems. In healthy cells, this helps them to recognize foreign bodies and protect against them, but when mutated, it can drive the subtype of SCLC. It's a bit rarer than those described above and is in 12% to 15% of cases. Fortunately, research is beginning to show that this type of SCLC may respond better to a class of experimental drugs called PARP inhibitors. These drugs, though still in trial, have been shown to stop the damaged DNA in cancer cells from replicating, preventing the spread of more cancerous cells.
SCLC Subtype-I
Finally, our last class of SCLC subtypes is SCLC-I. This stands for inflamed SCLC, and indicates that, rather than having higher levels of certain proteins, the cells have a lot of inflammation occurring, and a high level of immune cells within the environment. Because of this, research has shown that this subtype may have a stronger response to immunotherapy agents than other small cell lung cancers. This is a less common class of SCLC, found in about 10-15% of cases.
It is important to know that, when looking at how these sub-types may affect a person's prognosis, there was no difference noted in the length of a person's overall and progression free survival. This means that having one subtype over another doesn't seem to have an impact on how long they will live, or how serious their disease might be. As shown above though, it can impact what treatment types may be more effective, and can help oncologists think about which types of treatment they should try first. It can also useful when a person is considering clinical trials that they may want to join.
If you want to learn more about managing small cell lung cancer and what options are available, please reach out to us. GO2’s HelpLine is a free, one-on-one service that connects patients and caregivers with experienced staff who can provide guidance, resources, and, most importantly, hope!
Our Small Cell Lung Cancer Program can help to provide information and support at every step of the way, while LungMATCH can give you one-on-one, personalized information about treatments and trials for your cancer.
References:
- Baine MK, Febres-Aldana CA, Chang JC, Jungbluth AA, Sethi S, Antonescu CR, Travis WD, Hsieh MS, Roh MS, Homer RJ, Ladanyi M, Egger JV, Lai WV, Rudin CM, Rekhtman N. POU2F3 in SCLC: Clinicopathologic and Genomic Analysis With a Focus on Its Diagnostic Utility in Neuroendocrine-Low SCLC. J Thorac Oncol. 2022 Sep;17(9):1109-1121. doi: 10.1016/j.jtho.2022.06.004. Epub 2022 Jun 24. PMID: 35760287; PMCID: PMC9427708.
- Dahlstrom, Erin. “Advances in Small Cell Lung Cancer Classification.” MD Anderson Cancer Center, 25 Nov. 2024, www.mdanderson.org/cancerwise/advances-in-small-cell-lung-cancer-classification.h00-159702279.html.
- Schwendenwein A, Megyesfalvi Z, Barany N, Valko Z, Bugyik E, Lang C, Ferencz B, Paku S, Lantos A, Fillinger J, Rezeli M, Marko-Varga G, Bogos K, Galffy G, Renyi-Vamos F, Hoda MA, Klepetko W, Hoetzenecker K, Laszlo V, Dome B. Molecular profiles of small cell lung cancer subtypes: therapeutic implications. Mol Ther Oncolytics. 2021 Feb 6;20:470-483. doi: 10.1016/j.omto.2021.02.004. PMID: 33718595; PMCID: PMC7917449.
- The Asco Post Staff. “Study Identifies Four Unique Subtypes of Small Cell Lung Cancer.” Ascopost.com, 2026, ascopost.com/news/january-2021/study-identifies-four-unique-subtypes-of-small-cell-lung-cancer/. Accessed 30 Apr. 2026.