# Circulating Genomic Determinants of Treatment Failure in Hodgkin Lymphoma

> **NIH NIH R01** · STANFORD UNIVERSITY · 2022 · $640,898

## Abstract

PROJECT SUMMARY/ABSTRACT
PIs: Ash Alizadeh, M.D./Ph.D. & Maximilian Diehn, M.D./Ph.D.
Classical Hodgkin lymphoma (HL) is among the most curable human malignancies. However,
strategies to personalize HL therapies and to minimize long-term attendant toxicities of
chemotherapy are currently limited to baseline risk factors and imaging. This is due to our
incomplete understanding of targetable pathways and lack of good biomarkers. Because of the
low fraction of malignant cells in tumor tissue and consecutive technical challenges, the
landscape of HL is not well-defined.
Our long-term goal is to study the ability of baseline and dynamic risk factors, including genetic
mutations, circulating tumor DNA (ctDNA) and imaging studies (PET), to accurately predict
treatment outcomes in HL patients, and to provide a basis for individualized precision medicine.
Our central hypothesis is that clinical and biological heterogeneity in HL reflects distinct
genomic features that are noninvasively measurable using ultrasensitive ctDNA techniques, and
that refining early response assessment integrating interim PET and blood based methods
improves prognostication. We will test our hypotheses via three specific aims: (1) To
noninvasively define the genomic landscape of somatic variations in HL, and to determine the
relationship of genomic variants with biological heterogeneity at initial disease presentation, (2)
To associate molecular features at baseline and molecular response with ultimate therapeutic
outcome, and to integrate clinical and molecular biomarkers in a personalized dynamic risk
model for predicting HL outcomes, and (3) To functionally characterize novel mutations in
Interleukin-4 receptor (IL4R) resulting in gain-of-function IL4/STAT6 signaling, and to test the
utility of precision therapeutic targeting of these mutations.
If successful, our project will lead to novel ways to select better therapies for patients at highest
risk of failure, and to minimize toxicity for the majority of patients responding well to standard
therapy. Our innovative approach, in which we will combine blood-based methods for
genotyping and disease monitoring with imaging studies, will provide the basis for a
personalized treatment approach in HL.

## Key facts

- **NIH application ID:** 10364663
- **Project number:** 5R01CA257655-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Ash Arash Alizadeh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $640,898
- **Award type:** 5
- **Project period:** 2021-03-04 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10364663

## Citation

> US National Institutes of Health, RePORTER application 10364663, Circulating Genomic Determinants of Treatment Failure in Hodgkin Lymphoma (5R01CA257655-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10364663. Licensed CC0.

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