# Precision medicine for pancreatic cancer. Biomarker-guided drug delivery of platinum to tumors

> **NIH NIH R41** · BIOPLATINUM TECHNOLOGIES, LLC · 2024 · $338,828

## Abstract

This project proposes to study the effects of new platinum anticancer drugs in pancreatic cancer. We suggest
that the unique combination of two research areas - the implication of the glycocalyx in modification of the tumor
extracellular matrix and the correlation of sensitivity of certain platinum agents with the glycosaminoglycan (GAG)
status of the tumor – creates a unique profile amongst not just platinum agents but all currently used clinical
anticancer drugs. The critical unmet need in the treatment of pancreatic cancer is two-fold: 1) therapeutics to
effectively treat drug resistant disease and 2) predictive biomarkers to identify which patients will benefit most
from the available therapies. Among chemotherapeutic drugs, platinum derivatives have a major importance in
the therapeutic arsenal and oxaliplatin is a critical component of the FOLFIRINOX regimen for treatment of
pancreatic cancer. Our studies show that tumors expressing high levels of chondroitin-4-sulfate (C4S) can be
exploited for enhanced cellular accumulation and tumor delivery of the Phase II polynuclear platinum complex
(PPC, specifically Triplatin) in breast and ovarian cancer PDX models because of the high affinity of the highly
cationic drug to the highly negative GAGs, a property not shared by mononuclear oxaliplatin. Biomarkers to
predict durable response to this drug were not available then, and further development of Triplatin was
suspended. Recently, we have demonstrated that Triplatin could be superior to the main line platinums against
tumors expressing high levels of chondroitin-4-sulfate (C4S). C4S is a tumor-specific glycosaminoglycan (GAG)
attached to proteoglycans such as CD44, glypicans and syndecans, expressed on the cell surface and in tumor
stroma. The positive charge of Triplatin increases its affinity to the negatively charged GAG, which facilitates the
drug accumulation in the tumor cells and increases the level of Pt-DNA adducts. Interestingly, we noted that
carboplatin follows an opposite trend. Together, our studies support the premise that GAG levels can predict
carboplatin resistance and Triplatin sensitivity. Our central hypothesis is that high GAG levels in pancreatic
cancer can be exploited to increase Triplatin uptake and improve the efficacy of current treatment regimens. A
large research effort is ongoing to understand factors that influence the tumor response to therapy and to
evaluate strategies to overcome the treatment failure caused by intrinsic or acquired resistance. Studies aimed
at identification of the treatment targets for pancreatic cancer have mainly focused on mRNAs, miRNAs, and
proteins, while carbohydrates, such as GAGs, remain relatively unexplored. The non-template driven nature of
GAG biosynthesis involves a concerted action of multiple enzymes, complicating the analysis of expression at
the genomic/proteomic level and their role in clinical oncology. New technologies, such as glycan reductive
isotope labeling mass spect...

## Key facts

- **NIH application ID:** 10919357
- **Project number:** 1R41CA287830-01A1
- **Recipient organization:** BIOPLATINUM TECHNOLOGIES, LLC
- **Principal Investigator:** Nicholas Patrick Farrell
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $338,828
- **Award type:** 1
- **Project period:** 2024-08-06 → 2026-08-05

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10919357

## Citation

> US National Institutes of Health, RePORTER application 10919357, Precision medicine for pancreatic cancer. Biomarker-guided drug delivery of platinum to tumors (1R41CA287830-01A1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10919357. Licensed CC0.

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