2025-2026 MCW Radiation Oncology Annual Report - Flipbook - Page 22
2025-2026 Medical College of Wisconsin, Radia琀椀on Oncology Annual Report
Clinical Trials Driving Discovery and Innova琀椀on in
Head and Neck Cancer
Musaddiq Awan, MD
Associate Professor
Our mul琀椀disciplinary research team including Drs. Himburg, Zenga, Kearl,
Hema琀� and I, leverage novel clinical trial ini琀椀a琀椀ves to study hypofrac琀椀onated
radia琀椀on. Further, we use human 琀椀ssue samples and cu琀�ng-edge single-cell
bioinforma琀椀cs and co-culture approaches to understand the tumor-immune
microenvironment in head and neck cancers (HNC) and the influence of various
cancer therapies including radia琀椀on and immunotherapy.
Star琀椀ng at the bedside we have iden琀椀fied unique clinical scenarios and
completed two first-in-human clinical trials of novel radia琀椀on regimens for
HNC. On the DEHART trial, we tested dose-escala琀椀on using hypofrac琀椀onated
MR-guided radia琀椀on and immunotherapy to treat non-opera琀椀ve pa琀椀ents with
aggressive HNC. This trial showed excellent preliminary oncologic outcomes,
shi昀琀ing the pa琀琀erns of failure from locoregional to distant metasta琀椀c disease
even in pa琀椀ents with inoperable oral cancer. U琀椀lizing this MR-guided data, Dr.
Eric Paulson and I have mentored MD/PhD candidate Ryan Bonate on projects
leveraging daily quan琀椀ta琀椀ve MR changes to predict locoregional response to
HNC, which may be used in the future to adapt radia琀椀on dosage. More
recently, we completed the HyPR-HN trial, which tested a novel pre-opera琀椀ve radia琀椀on regimen for advanced oral
cancers, during which we performed serial biopsies including single-cell RNA sequencing to study changes in the tumor
and immune microenvironment during radia琀椀on. We discovered a novel gene signature for tumor-specific T cells
(Tprolif_tox) and found that cells carrying this signature are persistently ablated by radia琀椀on. (Fig 1)
We carried these novel trials findings back to the bench and are further inves琀椀ga琀椀ng the tumor-specificity of this
Tprolif_tox popula琀椀on u琀椀lizing bioinforma琀椀cs, single-cell co-culture experiments, and animal models. We are a琀琀emp琀椀ng
to use bioinforma琀椀cs approaches including whole exome sequencing, RNA sequencing and protein binding predic琀椀ons
using AlphaFold to predict the most likely
Last Day of RT
6 Weeks Post-RT Figure 1. Single-cell
Pre-RT
neoan琀椀gens that the Tprolif tox popula琀椀on
sequencing of
is reac琀椀ve against in a pa琀椀ent specific basis.
HNSCCs across
treatment timepoints
Further, using the Bruker Cellular Analysis
identifies depletion of
pla琀昀orm, we have sought to isolate
T cells expressing the
Tprolif_tox and other tumor-specific T cells
tumor-reactive
Prolif_Tox
from pa琀椀ent samples using single tumorsignature
T
(above, green). These
single T cell co-culture. Finally, we are
clonotypes (each
developing a pla琀昀orm to test the tumorrepresented by a
specificity of this popula琀椀on in vitro (with
different color) do not
return to the TME
and without radia琀椀on) using the MOC1 and
post-radiation (below).
MOC2 mouse models.
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