ABOUT THIS EPISODE

DLL3 is emerging as a promising new target for neuroendocrine cancers. In this episode, Dr. Rohit Thummalapalli, medical oncologist at Memorial Sloan Kettering Cancer Center, explains what DLL3 is, how it works, who might benefit, and what current clinical trials are teaching us. He breaks down the science, treatment options, and future directions in a way that is clear, approachable, and designed to help patients and families better understand this developing area of care.

TOP TEN QUESTIONS 

Understanding the Basics

1. What is immunotherapy? How does immunotherapy work?

2. What is DLL3? How does it work in the context of neuroendocrine cancer?

3. How is DLL-targeted therapy similar to or different from other types of immunotherapy? Is there evidence that one works better than another?

Indications, Use, Access & Availability

4. When is DLL3 used in neuroendocrine cancers? 

• What types of neuroendocrine cancer might express DLL3?
• How does someone know if this is a potential treatment option for them?
• At what point in a patient’s treatment journey might DLL3 be considered?
• How and where DLL3 is available for neuroendocrine cancer patients? What are other ways, if any, to access DLL3?

Testing for DLL3 Expression

5. How does someone find out if their tumors express DLL3 receptors? 

• How & where is DLL3 expression tested? It it tested through tissue samples, imaging, or something else?
• Is there a minimal level of DLL3 expression that is required to receive the treatment? (Does the threshold vary by trial?)
• Does the level of DLL3 expression differ by institution? 
• Does the level of DLL3 expression predict how well someone might respond to treatment?
• Can the tumor expression of DLL3 vary from tumor to tumor? Can it vary over time, meaning can tumors gain or lose expression?
• Do you measure the DLL3 expression following treatment?

Treatment Considerations

6. How effective is DLL3-targeted therapy in neuroendocrine cancers? What is the goal of treatment with DLL3 – shrinkage, stabilization, symptom relief? How long is it expected to work? How do you measure the response to DLL3 treatment? 

7. Can DLL3 be combined with other therapies? 

Decision-Making and Patient Counseling

8. How do you decide when to offer DLL3 for someone with neuroendocrine cancer? 

• What factors or prior treatments might make someone ineligible for DLL3 therapy?
• Could receiving DLL3 exclude a patient from other treatments or clinical trials?

9. How do you counsel patients who are considering DLL3? 

•  What should they know about how the treatment is given, possible side effects, and what’s known (or unknown) about long-term safety?
• What should one expect in terms of frequency of visits, hospitalization and side effects?
• Can someone still work while receiving DLL3?

Looking Ahead

10. What are the key questions you hope to answer about DLL3 in the next year? What do you hope to learn over the next 3 to 5 years?

ABOUT DR. ROHIT THUMMALAPALLI 

Rohit Thummalapalli is a gastrointestinal medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center specializing in clinical care and research in patients with neuroendocrine and biliary tract cancers. Originally from Florida, Dr. Thummalapalli completed medical training at Harvard and Johns Hopkins before arriving at MSK as a medical oncology fellow in 2021, and started on faculty in 2024.

For more information, visit https://www.ncf.net/podcast/48

For more information, visit NCF.net.