From the Guidelines
The significance of anti-Delta-like 3 (DLL3) lies in its potential as a therapeutic target for small cell lung cancer (SCLC) and other neuroendocrine tumors, with emerging therapies such as tarlatamab showing promise in clinical trials. The DLL3 protein is highly expressed in SCLC and other neuroendocrine tumors, but minimally present in normal tissues, making it an ideal target for cancer therapy 1. DLL3 is involved in the Notch signaling pathway that regulates cell differentiation and proliferation.
Current Therapies
- Tarlatamab, a bispecific T-cell engager, has been approved by the US Food and Drug Administration (FDA) for the treatment of patients with relapsed SCLC, with a recommended phase 2 dose of 10mg 1.
- Other emerging anti-DLL3 therapies include AMG 757 and CAR-T cell therapies targeting DLL3.
- Rovalpituzumab tesirine (Rova-T), an antibody-drug conjugate that targets DLL3, had its development discontinued after disappointing clinical trial results 1.
Importance of DLL3 Expression
- Patients with high DLL3 expression may be better candidates for these therapies, so testing for DLL3 expression is recommended before considering treatment.
- The expression of DLL3 in SCLC and other neuroendocrine tumors makes it a potential biomarker for targeted therapies.
Clinical Trials
- Ongoing clinical trials are investigating the efficacy of anti-DLL3 therapies in SCLC and other neuroendocrine tumors.
- The results of these trials will provide further insight into the potential of anti-DLL3 therapies as a treatment option for patients with SCLC and other neuroendocrine tumors.
From the Research
Significance of Anti-Delta-like 3 (DLL3)
- DLL3 is an inhibitory Notch ligand that is highly expressed in small cell lung cancer (SCLC) and other neuroendocrine tumors, but minimally expressed in normal tissues 2.
- The high expression of DLL3 in SCLC makes it a potential therapeutic target for the treatment of this disease 2, 3, 4.
- Several DLL3-targeted therapies are being developed, including antibody-drug conjugates (ADCs), T-cell engager (TCE) molecules, and chimeric antigen receptor (CAR) therapies 2, 4, 5.
Prognostic Value of DLL3
- High DLL3 expression levels are associated with worse overall survival in SCLC patients 3.
- DLL3-low/TTF-1- is a distinct molecular subgroup of SCLC with optimal prognosis 3.
- DLL3 expression levels can vary during the course of therapy, suggesting therapy-based alterations 6.
DLL3-Targeted Therapies
- Rovalpituzumab tesirine is a DLL3-targeting ADC that has shown promise in the treatment of SCLC, but its development was halted due to a lack of efficacy in phase 3 studies 2, 4.
- FZ-AD005 is a novel DLL3-targeted ADC that has shown potent antitumor activity in preclinical models and is expected to provide clinical benefits for the treatment of patients with SCLC 5.
- Other DLL3-targeted therapies, such as tarlatamab and AMG 119, are also being developed and have shown promising results in preclinical and clinical studies 4.