Télévie: Determination of the genes implicated in intrinsic resistance to proton beam therapy for the treatment of pancreatic adenocarcinoma

Pancreatic adenocarcinomas are one of the most aggressive solid cancers
with a median survival of less than 12 months. The best treatment in this
type of pathology is the surgical resection but in most cases, the diagnosis
is made after the tumor has already spread to the adjacent organs. In this
case, only chemotherapy associated with radiotherapy is possible, but this
combination shows limited effects and displays an important toxicity for the
patient. Recently, proton beam therapy has become an important alternative
in the treatment of cancer by decreasing toxicity to surrounding organs
compared to conventional radiotherapy. The interest of its use in the
treatment of pancreatic adenocarcinoma is important by limiting the side
effects on the healthy tissues such as the stomach, the liver or the kidneys.
In this study, we propose to determine the genes involved in the resistance
of pancreas tumors to proton beam therapy and thus to better determine the
doses to be administered to patients and the chemotherapies to be used in
combination. To reach our objective, we will use in vitro models of
pancreatic adenocarcinomas in which we will screen more than 18,000
genes potentially involved in these resistance mechanisms by using the
CRISPR / Cas9 technique. Finally, this work will allow us to better
understand by which mechanisms the pancreatic adenocarcinomas respond
to the proton therapy but also to propose combinations with chemotherapies
to bypass their intrinsic resistance to protons.