# Cancer and stromal metabolic reprogramming drives chemotherapy resistance in human models of pancreatic cancer

> **NIH NIH U54** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2024 · $161,750

## Abstract

Abstract
Pancreatic cancer patients show an extremely poor prognosis, which is at least in part due to poor response to
the current standard-of-care chemotherapies. While pancreatic tumors present an inadequate response to
chemotherapy, exposure to chemotherapy leads to development of acquired resistance. The response and
resistance to chemotherapies are modulated by signaling and metabolic alterations in tumor cells and companion
changes in the immune and non-immune stroma. Major advances in (a) understanding signaling responses of
cancer cells and stroma to therapy, (b) understanding metabolic adaptations to signaling and environmental
stressors, (c) development of novel therapeutic combinations to improve long-term response to current
standards-of-care chemotherapies, and (d) coordinating research/translation efforts by NCI leadership, will
provide unparalleled advances in targeting/preventing acquired therapy resistance. The ARTNet Center for
Pancreatic Cancer (ACPC) intends to achieve these objectives through an integrated research theme that
combined investigations into the metabolic and signaling mediators of acquired resistance in tumor cells and
stromal remodeling in pancreatic cancer will lead to novel effective therapies to improve the patient prognosis.
Research within ACPC will be fostered through sound guidance from leadership, IAC, EAC, ARTNet network
and NCI program. The overall goal of the Center is to study innovative hypothesis-driven mechanisms of
metabolic and signaling alterations in tumor cells and tumor-stromal metabolic crosstalk that contribute to
acquired therapy resistance in pancreatic ductal adenocarcinoma (PDAC). We hypothesize that our unique
leadership team, outstanding expertise of project and core leaders, singular set of technological capabilities and
resources, operational design, and strong institutional support of the ACPC will drive transformative advances
in the acquired therapy resistance field that will be in alignment with the other ARTNet members and NCI’s
mission for the program. Providing novel insights into the mechanistic aspects of the signaling and metabolic
mechanisms, the proposed basic and translational studies will ultimately drive the development of novel
therapeutic combinations that can change the clinical course of cancer therapy. This will be achieved through
the following Specific Aims: Aim 1. Investigate novel mechanisms of acquired resistance at the interface of tumor-
stromal metabolic cross talk and examine the preclinical efficacy of identified targets to improve the therapeutic
response against pancreatic cancer. Aim 2. Provide robust and innovative toolsets and resources to investigate
and validated mechanisms of acquired therapy resistance. Aim 3. Facilitate a systems-level mechanistic
understanding of acquired therapy resistance mechanisms.

## Key facts

- **NIH application ID:** 11073933
- **Project number:** 3U54CA274329-03S1
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** Pankaj Kumar Singh
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $161,750
- **Award type:** 3
- **Project period:** 2022-09-20 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11073933

## Citation

> US National Institutes of Health, RePORTER application 11073933, Cancer and stromal metabolic reprogramming drives chemotherapy resistance in human models of pancreatic cancer (3U54CA274329-03S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11073933. Licensed CC0.

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