UCLA Journal of Radiation Oncology January 1, 2022 - Flipbook - Page 33
UCLA RADIATION ONCOLOGY JOURNAL
BEST OF: ASTRO 2021
The following three presentations from ASTRO showcase
the research, hardwork, and collaboration efforts of our
UCLA Radiation Oncology faculty and residents.
Identifying Unique Genetic
Variants To Overcome Cancer
Treatment Barriers
UCLA researchers add monoclonal antibody
to target oropharyngeal cancer in HPVpositive patients with KRAS gene variant
FINDINGS
Dr. Robert Chin, a radiation oncologist
with UCLA Jonsson Comprehensive Cancer
Center, will describe recent research on
personalized treatment for HPV-associated
oropharyngeal cancer – particularly for
patients with an inherited variant KRAS
gene – during a panel discussion on
radiation and cancer biology at ASTRO, the
annual meeting of the American Society for
Radiation Oncology. This research represents
current and future efforts to identify patients
uniquely sensitive to innovative targeted
treatments.
The research builds on studies led by
Dr. Joanne Weidhaas at UCLA Jonsson
Comprehensive Cancer Center, who found
that about 16% of head and neck cancer
patients have inherited a variant KRAS
gene. When these patients receive standard
chemoradiation treatments for their HPVpositive squamous cell cancers of the
oropharynx, they have both worse toxicity
and worse rates of cancer control, Chin
said. However, these poor outcomes may be
reversed with the addition of a short course
of cetuximab.
“In standard clinical practice, tumors are
assumed to be different, but patients mostly
uniform,” Chin said. “Thus, we spent a lot of
energy analyzing tumors. However, we have
since come to understand that our body’s
own immune system is crucial in making
treatments effective. Matching the right
body to the right treatment may make our
treatments less toxic and more effective.”
Chin said UCLA researchers are conducting
a clinical trial in which patients with this
unique combination – having both the KRASvariant and HPV-positive squamous cell
oropharyngeal cancer – are randomized to
either standard of care treatment or standard
of care plus cetuximab. “We think this
approach of identifying unique clusters of
patients may be a way for us to design new
treatments that are more personalized and
effective,” he said.
BACKGROUND
In 2006, researchers discovered the KRASvariant, an inherited genetic mutation found
in up to 25 percent of people with cancer.
The variant, a biomarker that disrupts a class
of important regulators called microRNAs,
has been shown to predict response to
cancer therapy for many cancers.
Chemotherapy and radiation therapy, the
current standard-of-care modalities for
HPV-positive squamous cell carcinoma
of the oropharynx, typically have about a
5-10% treatment failure. The failure rate
is much higher in KRAS-variant patients.
However, the addition of a short course of
the monoclonal antibody cetuximab has
been found to reverse this effect. Weidhaas’
research team found that cetuximab may
be working by helping the immune system
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