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Researchers have found a promising biomarker that may help doctors predict which patients with extensive-stage small cell lung cancer (ES-SCLC) are most likely to respond to tarlatamab. This targeted immunotherapy is possible because of new insights into DLL3 biology, partially funded by NFCR supporters.

What is extensive-stage small cell lung cancer (ES-SCLC)?

Extensive-stage small cell lung cancer (ES-SCLC) is an advanced type of small cell lung cancer (SCLC) where the cancer has spread (metastasized) from one lung to other areas of the body. After initial first-line treatment, patients experience resistance within one year. Improved therapeutic options are an unmet need for these patients.

What is DLL3?

DLL3 is a protein that appears in large amounts on small cell lung cancer cells. This makes it a good target for new precision immunotherapies.

What was discovered?

Scientists studied circulating tumor cells (CTCs), which are cancer cells that enter the bloodstream. They found that patients with higher levels of DLL3 on these cells before treatment were much more likely to benefit from tarlatamab. Those with low DLL3 levels rarely responded.

Why This Matters for Patients and Clinicians

Tarlatamab is a bispecific T-cell engager approved for ES-SCLC. It works by helping a patient’s cancer-fighting immune cells (T cells) attack cancer cells that express DLL3, a protein often found on SCLC cells.

But not all patients respond the same way. This study shows that a simple blood test measuring DLL3 in CTCs before treatment could help doctors identify who is most likely to benefit, making therapy decisions more personalized.

In this initial group, the test had high accuracy at correctly identifying which patients would respond and which would not.

Potential Impact of This Research

Using a liquid biopsy, which is a blood test that analyzes tumor cells, could give doctors a non-invasive way to match immunotherapy to each patient’s tumor biology.

This is an important move toward precision oncology for SCLC, a cancer that has usually had few biomarkers to help guide treatment choices.

If larger studies confirm these results, this approach could lead to better outcomes and fewer unnecessary treatments and side effects.

Powered by Long-Standing NFCR Support

This breakthrough is the result of a long partnership between NFCR and Dr. Daniel A. Haber. Dr. Haber is a renowned leader on genetic abnormalities of cancer, from inherited mutations (with familial predisposition) to mutations that are acquired by tumors themselves. With NFCR funding since 2000, his research aims to guide targeted drug therapies.

 His pioneering work in circulating tumor cell (CTC) technology has changed how scientists study cancer in real time using a minimally invasive blood sample.

Thanks to NFCR’s early and ongoing support, Dr. Haber developed new tools that help researchers predict treatment response, track disease progression, and advance precision medicine. Discoveries like this show the lasting value of donor support for bold, high-risk research that improves cancer care.