# Somatostatin receptor 2 (SSTR2) antibody-drug conjugate for pancreatic neuroendocrine tumor (PanNET) therapy

> **NIH NIH R21** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $199,497

## Abstract

Pancreatic neuroendocrine tumors (PanNETs) are increasing in incidence, and 40-95% of them
are metastatic at the time of initial diagnosis. Despite various complex management strategies for
neuroendocrine liver metastases, surgery is the only treatment that offers potential for cure. There
is a critical need to develop new therapeutic options to reduce PanNETs progression. We have
discovered that PanNETs are deficient in Notch signaling, and reinstitution of this pathway alters
the malignant phenotype. Therefore, there is a need for an effective Notch activator as a
therapeutic agent against PanNETs. We hypothesize that the induction of Notch signaling with
small molecule compounds will provide an effective strategy to treat patients with PanNETs. High-
throughput screening for Notch pathway activators identified a natural compound originating from
marine sponges (DHN-III-14) capable of inhibiting PanNETs proliferation and altering the
neuroendocrine (NE) cancer phenotype. To improve therapeutic efficacy, we propose to
conjugate the drug candidate with an antibody that specifically binds to somatostatin receptor
(SSTR2) which is overexpressed on the surfaces of PanNETs cells. Such antibody-drug
conjugate (ADC) can selectively deliver a lethal agent to tumor cells and minimize side effects to
patients. To delineate the antitumor efficacy of the ADC, we will use the in vitro PanNET cell
cultures and the in vivo preclinical mouse model of liver metastases. If the anticancer efficacy will
be confirmed in the preclinical models, this will be the first ADC toward targeted therapy for
PanNETS.

## Key facts

- **NIH application ID:** 9895383
- **Project number:** 1R21CA226491-01A1
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Renata Jaskula-Sztul
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $199,497
- **Award type:** 1
- **Project period:** 2020-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9895383

## Citation

> US National Institutes of Health, RePORTER application 9895383, Somatostatin receptor 2 (SSTR2) antibody-drug conjugate for pancreatic neuroendocrine tumor (PanNET) therapy (1R21CA226491-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9895383. Licensed CC0.

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