# Novel Strategies to Eliminate Resistance to B-cell Receptor Inhibitor Therapy in Lymphoid Malignancies

> **NIH NIH K23** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $180,360

## Abstract

PROJECT SUMMARY/ABSTRACT
Overview: The goal of this award is to provide Dr. Deborah Stephens, with training and mentored research
experiences that will facilitate her transition into the role of an independent investigator in experimental
therapeutics and mechanisms of resistance to cancer therapies for patients with lymphoid malignancies. Her
long-term career goal is to become a clinical/translational investigator who contributes new knowledge to the
field, impacts how we think about lymphoma, and helps to improve patient outcomes.
Research: Relapsed/refractory chronic lymphocytic leukemia (CLL) and non-Hodgkin’s lymphomas (NHLs), are
common, incurable malignancies that contribute significantly to cancer mortality. Recently, novel targeted
therapies have improved clinical outcomes. However, patients who develop therapy resistance have very poor
outcomes. The proposed research aims to understand, prevent, and overcome this therapy resistance. This
proposal includes two clinical trials that involve rational combination therapies with the aim to mechanistically
prevent treatment resistance. Longitudinal samples from patients treated on the proposed clinical trials will be
analyzed by targeted and whole exome sequencing. A novel computational tool developed at the University of
Utah will be used to study the evolution of sub-clonal cancer cell populations. The proposed trials introduce two
novel and rational combination therapies that could change the current paradigm of CLL/NHL therapy.
Correlative studies will provide new insights into the mechanisms governing response and resistance to BCR
inhibitor combinations, and identify biomarkers for early identification of patients at risk of relapse. The
combination of rationally designed early clinical trials with molecular studies to identify the causes of response
and resistance will provide Dr. Stephens with the training needed to become a successful clinical translational
researcher in lymphoid malignancies and provide the basis for R-level funding to gain academic independence.
Career Development Plan/Environment: Dr. Stephens is an oncologist with a strong foundation in translational
research in the field of lymphoid malignancies. The K23 graduate coursework, targeted training, seminar
attendance, and mentored research experiences will provide the skills and experiences Dr. Stephens needs to
become an independent investigator in lymphoid malignancies. During this award, Dr. Stephens will acquire new
content area knowledge in genomic and bioinformatics analysis. She will gain practical skills in clinical trial
design, management, genomic analysis, and working collaboratively with an extensive multi-disciplinary
research team. Dr. Stephens has assembled a highly experienced and internationally-recognized mentoring
team, who will provide guidance in translational cancer research. The Huntsman Cancer Institute, an NCI-
designated Comprehensive Cancer Center and the University of Utah provide a rich en...

## Key facts

- **NIH application ID:** 10003969
- **Project number:** 5K23CA212271-05
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** DEBORAH STEPHENS
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $180,360
- **Award type:** 5
- **Project period:** 2016-09-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10003969

## Citation

> US National Institutes of Health, RePORTER application 10003969, Novel Strategies to Eliminate Resistance to B-cell Receptor Inhibitor Therapy in Lymphoid Malignancies (5K23CA212271-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10003969. Licensed CC0.

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