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NIH grant 1P01CA314921-01: Metabolic Imaging of Anaplastic Thyroid Cancer to Assess Treatment Response
Institute: {'code': 'CA', 'abbreviation': 'NCI', 'name': 'National Cancer Institute', 'admin_org_id': '12500008', 'admin_funding_url': ''}. PI: James A Bankson. Award: $490611.
Start: 2026-09-18T00:00:00.
ABSTRACT: Project 3
Aggressive variants of thyroid carcinoma such as anaplastic thyroid cancer (ATC) are associated with a high
rate of locoregional and distant metastasis, decreased treatment response and poor patient survival. There are
currently no effective systemic agents specifically tailored to these aggressive solid tumors. The most recently
approved targeted agent combination (BRAF-MEK inhibitors) is effective only in a subset of tumors and
demonstrates limited response durability. New therapeutic strategies and novel methods to monitor disease
response to therapy or progression are significantly unmet needs to improve outcomes in patients with ATC. In
this project, we will assess new approaches to treating ATC alongside emerging methods that may provide
earlier indications of response to therapy. Hyperpolarized (HP) [1-13C]-pyruvate is a clinically translatable
metabolic contrast agent that enables characterization of tumor metabolism (aerobic glycolysis) by magnetic
resonance. We have developed a translational pipeline for assessing metabolic changes due to perturbations in
vitro in cell suspensions, in vivo in orthotopic xenograft models of thyroid cancer, and in patients. Because
pyruvate is quickly metabolized, signal from the HP “spin label” decays to an undetectable thermal equilibrium
after only a few minutes, and the stable 13C isotope label produces no radiation, HP pyruvate is well tolerated
and can be used repeatedly over the course of treatment to characterize dynamic changes in tumor metabolism
as the tumor progresses or responds to therapy. The overall goal of this project is to characterize metabolic
changes in ATC when treated with combinations of targeted therapies (Project 1, Core B) and cellular
immunotherapy (Project 2). The long-term goal is to develop a new therapeutic paradigm that leverages
feedback from HP MRI to optimize the treatment course based on changes in tumor metabolism. Our overall
hypothesis is that metabolic imaging with HP pyruvate can provide a minimally invasive mechanism for
identifying early indications of therapeutic response and resistance. In Aim 1, we will assess metabolic
changes in response to BRAF-targeted therapy, in cell lines with known sensitivity and resistance to BRAF
inhibitors. Early indication of resistance to BRAF inhibitors would facilitate an earlier transition to alternative
approaches or other therapeutic options. In the second aim, we will evaluate changes in HP pyruvate metabolism
in patients with ATC that are treated with BRAF inhibitors. To explore the potential for cellular immunotherapy in
the treatment of patients with ATC in Aim 3, we will characterize metabolic changes in subsets of T cells in
response to activating agents and tumor cells. We will also assess changes in tumor metabolism in cells that are
treated with combinations of cellular immunotherapy and targeted therapies. Throughout these aims, we will
compare the metabolic phenotype observed through HP MRI with metabolic gene signatures (Project 4, Core
C).document fetched 2026-09-27 02:45