YSM Issue 93.2

Genomics / Clinical Research
FEATURE
loop was done for everything seen on the
Angiosarcoma Project Website.
Once the project was launched,
high participation rates were almost
immediate. After joining the project,
participants could give consent to share
online medical records, and send in saliva,
blood, and tumor samples. Throughout
the process, research updates were
continuously disseminated to patients
through the online platform, allowing
patients to provide feedback.
Through the project, over seventy tumor
samples were obtained, allowing for large-
scale whole exome sequencing, a method
that sequences protein-coding regions
in the genome. Painter’s team could also
access medical history data. Integrating
these types of data enabled robust analysis
of multiple subclasses of angiosarcoma.
Sequencing data obtained for patient
tumor-samples elucidated three genes––
PIK3CA, GRIN2A, and NOTCH2––that
were consistently altered in angiosarcoma.
Subsequent analysis of mutation frequency
indicated that the PIK3CA gene is one
of the most commonly mutated in breast
angiosarcoma. This finding is clinically
relevant, pointing to PIK3-alpha inhibitors
as a potential therapeutic route for primary
breast angiosarcoma treatment. Finally,
Painter looked at the mutational burden,
which is the number and type of somatic
mutations in the DNA of cancer cells.
She found that the number of mutations
in head-neck-face-scalp (HNFS)
angiosarcoma is significantly enriched, in
a pattern consistent with UV-light induced
DNA damage. This finding suggests that
this angiosarcoma cohort might respond
well to immune checkpoint inhibitors.
The novel findings produced by this
project are already making an impact. “[Our
project is] decoupled from the publication
process entirely, so we’ve been releasing
data for well over a year,” Painter said. By
presenting at Clinical Oncology Alliance
Meetings and to The American Society of
Clinical Oncology (ASCO), Painter was able
to share her results with clinical researchers.
As a result, “There are three different groups
working on drafting clinical trials. One
of them was able to get angiosarcoma as a
cohort in an existing checkpoint inhibitor
study,” she said. Painter also mentioned that
two additional studies are being currently
developed based on her data. Painter also
anticipates the potential for pre-clinical
researchers, who are not necessarily
studying angiosarcoma, to see results from
her project that involve pathways or genes
of interest and to become interested in
partaking in angiosarcoma research.
The Angiosarcoma Project is a significant
step forward for patient-partnered
research. Painter demonstrated how a
sincere and deep level of collaboration
between patients and researchers can
stimulate the most meaningful and
translationally relevant results.
Challenges and future directions for
PPI in research
Successful patient-partnered research,
like the Angiosarcoma Project, is
popularizing PPI. This is reflected in an
increasing number of PPI studies, as well
as the proliferation of grant applications
that require researchers to describe how
they plan to involve patients of the public
in their studies. As this approach becomes
more popular, it is important to consider
current challenges and future directions
of this type of research.
The single greatest challenge to expanding
PPI in research is scientists’ lack of clarity
on the most effective ways to facilitate
engagement with patients. Painter, when
discussing the Angiosarcoma Project,
noted that building the project, “was
much easier than the metastatic breast
cancer project because we were going off
a vision.” For her, the metastatic breast
cancer project provided a scaffold that
was subsequently utilized to build out the
Angiosarcoma Project in a way that was
tailored to that specific patient community.
Painter’s insight highlights how researchers
can draw from previous studies in order to
guide and facilitate their own PPI studies.
Painter notes that it is imperative to adapt
each project to the needs of the specific
disease community, but that having a pre-
existing vision is still highly useful.
As PPI expands, ensuring a continued
commitment to patient diversity is
critical. One way to facilitate this is by
ensuring that patient-advocates from
diverse backgrounds are included, since
these advocates are the cornerstone of
research outreach efforts.
Finally, while most research integrating
a patient-centered approach involves
clinical research or translational research
that makes use of patient samples,
there is a strong argument for patient-
public involvement in pre-clinical and
basic science research as well. Emma
Dorris is a molecular biologist at The
University College Dublin who also leads
a PPI initiative for Arthritis Research.
She argues that PPI elevates research by
increasing the relevance and impact of
projects. Dorris believes that patients can
provide novel insights that direct scientists
towards areas of a disease’s biology that
haven’t been previously studied. While
in a wet-lab setting patients cannot be
involved in the data collection or analysis,
there is a clear and meaningful space for
their involvement in defining research
questions and goals. In order to encourage
researchers in preclinical labs to effectively
integrate PPI, experts recommend training
in patient-communication, as well as
top-down incentives and infrastructure
support from research institutions.
Patient-partnered research holds immense
promise for biomedical science. It offers to
improve the quality and relevance of research,
improve relationships between researchers and
the public, overcome boundaries to studying
rare diseases, and help ameliorate racial
and socioeconomic inequalities in research.
As PPI studies continue to expand, critical
examination of what types of engagement are
most effective will be necessary. ■
Burns, J. A., Korzec, K., & Dorris, E. R. (2019). From intent to implementation: Factors affecting public
involvement in life science research. doi: 10.1101/748889
Jayadevappa, R. (2017). Patient-Centered Outcomes Research and Patient-Centered Care for Older
Adults. Gerontology and Geriatric Medicine, 3, 233372141770075. doi: 10.1177/2333721417700759
Pii, K. H., Schou, L. H., Piil, K., & Jarden, M. (2018). Current trends in patient and public involvement in
cancer research: A systematic review. Health Expectations, 22(1), 3–20. doi: 10.1111/hex.12841
Staniszewka, S. (2020). A patient–researcher partnership for rare cancer research. Nature Medicine,
26(2), 164–165. doi: 10.1038/s41591-020-0766-y
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IMAGE COURTESY OF PXHERE
September 2020 Yale Scientific Magazine 25