Description of the PhD thesis project
Squamous cell carcinomas (SCCs) may originate
from various locations in the body, are sometimes related to HPV (Human
Papilloma Virus) infection and are shown to harbour similar molecular
alterations justifying a common therapeutic strategy.
Based on the literature and preliminary
results, we hypothesize that SCCs share common molecular features that support
the clinical development of an immunotherapy in combination with an epidrug. In
the frame of an ERAPERMED project supplemented by a funding from the Agence de
la Recherche contre le Cancer, we set up the PEVOSQ basket trial that evaluates
this combination in SCC patients. The trial received regulatory approval and
started including patients in September 2020.
The PEVOSQ prospective phase II basket trial
aims to evaluate the antitumor activity of pembrolizumab in combination with
vorinostat in patients with late stage SCC of the head and neck, cervix, lung,
anus, vulva and penis. Multi-omics integrative analysis will be performed on
samples collected at different time points during patient treatment and
follow-up in order to better understand the mechanisms of response or
resistance to this combination.
More specifically, the multiomics analyses
- WES (Whole Exome Sequencing) on DNA from
patients’ tumors and blood (PBMC) at baseline,
- RNAseq on tumor samples for RNA analysis
from patients at baseline,
- Global and genome-wide epigenetic analysis
to evaluate the possible role of key epigenetic modifications as predictors of
response to investigational drugs, (techniques under discussion, and may
include DNA-methylome-genomic-scale, ChIP-seq, ATAC-seq)
- Circulating HPV DNA by droplet digital dPCR
(ddPCR) on HPV positive patients to assess the predictive value of circulating
International, interdisciplinary &
intersectoral aspects of the project
The project is a European project that
includes a multidisciplinary international consortium.
In the PEVOSQ clinical trial, SCC patients
with different types of squamous cell carcinomas (SCCs) are treated with a
combo of immunotherapy with an epidrug. It will allow to run integrative
molecular and immune analyses to better understand the mechanism of response
and resistance to immune-checkpoint blockade in combination with an epidrug.
It involves European teams actively involved
in translational research and with complementary skill and expertise in cancer
epigenetics, bioinformatics, cancers, pharmacogenomics and medical oncology.
The proposal is at the frontier of two
complementary domains which are
i) bioinformatics and data analysis
ii) (epi)genetics and cancer biology.
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