# Preclinical Models and Therapeutics Core

> **NIH NIH P01** · MAYO CLINIC ARIZONA · 2021 · $147,916

## Abstract

Contact PD/PI: Rimsza, Lisa Shared-Res-Core-003 (458)
The Preclinical Models and Therapeutics Core (PMTC) will generate/assemble and characterize a wide array
of patient derived tumor xenograft (PDTX) models and patient derived organoids (PDO). We will use PDTX
models to conduct in vivo preclinical animal studies described in Projects 1, 2, 3 and 4. This will allow for
efficient and consistent evaluation of the efficacy of the novel therapeutic approaches proposed in each of the
Projects. Translational cancer research has been greatly facilitated by the demonstration that human tumors
can be grown as xenografts in immunocompromised mice, and the use of PDTX has significantly increased the
public knowledge of cancer biology and improved the preclinical evaluation and predictability of investigational
drugs. Historically, as high as 85% of drugs with in vitro activity have failed in human studies. More importantly,
PDTX were proven to maintain many of the features of the original patient tumors, including expression
phenotypes, genomic landscape and tumor heterogeneity and intrinsic properties such as their ability to
colonized/disseminate into specific organs. This allows for the design and implementation of highly informative
pre-clinical trials, capable of anticipating the responses of individual cancer patients. PDTX serve as a
renewable, quality-controlled tissue resource for preclinical evaluation of novel treatment regimens and will be
the principal platform for evaluation of the efficacy of the targeted therapies, outlined in the Projects of this
current application. Although many PDTX have been established from solid cancers, PDTX from hematological
disorders are still rare and no comprehensive libraries exist. Here we will focus on the generation and
characterization of PDTX from DLBCL and T-cell lymphoma, which remains an unmet clinical need. It is
now recognized that the poor therapeutic success in this arena is largely due to the complex heterogeneity of
these neoplasms, as well as, in the case of mature T-cell neoplasms, the lack of “bona fide” cell lines or
reproducible and informative mouse models. Both PDTX and derived 2D/3D in vitro models will be molecularly
profiled (WES/target sequencing, total RNA-Seq and ERBBS) and validated using functional approaches.
Preclinical testing will be available using a battery of conventional and novel compounds. PDTX are particularly
useful for in vivo mechanistic studies through the use of PDOs, and the information from these studies will be
instrumental in understanding the biology, stratification criteria and response(s) to the targeted therapies
described in the Projects. PMTC will closely interact with the Biostatistics and Bioinformatics and
Functional Genomic Cores for genomic and functional analyses. The PMTC proposes 2 Specific Aims in
support of all 4 Projects: (1) Generate and characterize PTDX and derived PDO and (2) provide
comprehensive planning, preparation and coordination of in ...

## Key facts

- **NIH application ID:** 10237167
- **Project number:** 5P01CA229100-04
- **Recipient organization:** MAYO CLINIC ARIZONA
- **Principal Investigator:** Giorgio Inghirami
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $147,916
- **Award type:** 5
- **Project period:** 2018-09-19 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10237167

## Citation

> US National Institutes of Health, RePORTER application 10237167, Preclinical Models and Therapeutics Core (5P01CA229100-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10237167. Licensed CC0.

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