Research Areas:
Personalized medicine requires the understanding of
the tumor, vicinity, host and unknown factors. It remains a challenge to
decide what are the relevant targets that drive
tumor growth that should be prioritized for therapy.
PDX (Patient-derived
xenografts) are tumor models in which a portion of a patient’s tumor is
transplanted in immunodeficient mice (NSG/NRG), and allowed to propagate
without any in vitro manipulation and are widely used today in the field of
personalized medicine. The tumors grown in mice faithfully reflect the heterogeneity,
molecular and histopathological signatures of the original tumor, and their
drug response profiles correlate with
clinical response. Thus, PDX are considered to be reliable translational
oncology platform and have become critical elements in preclinical drug
development.
Our lab generate a repository of PDX models from various type of solid tumor; both from common types (like colon, breast,
pancreas, head and neck , gastric, ovarian etc.) as well as
rare types (like bloom cancer, carcinosarcoma, neuroendocrine carcinoma) or base on a specific clinical unmeant need
(resistance to specific targeted therapy).
Our repository contain a collection of >500 tumor
samples, and more than 200 PDX models are available for research.
In
addition, tumor samples in the labinclude the corresponding formalin-fixed tumor tissue, frozen human
material, patient's clinical data, and for some also patient's blood
samples.
The lab is
focusing on three main applications:
1. Personalized
Medicine:
"bedside - to bench - to bedside”
PDX
model with identification of tumor mutations and
alterations,
allow to test the efficiency of several targeted-therapies (predicted by
mutation profile), thereby allowing the identification of a personalized
therapeutic regimen.
Information found in PDX models may suggest the physician alternative
treatment options that could tailor a better treatment for the specific patient (with
recognition of the limitations associated with a mouse model).
2. Research projects in the lab:
2.1.
Finding novel combination of anticancer therapies to
improve efficacy and overcome resistance
2.2. Establish humanized PDX mice models
This project tries to "humanize" the immune-system of the immune deficient mice. The mice develops the patient own tumor
and the same patient own immune system. This model better represent the complexity of the disease in patients, and allow to test treatments based
on the interactions of the tumor with the immune system ("I/O” approaches).
Also, the model allows to test the development of immune resistance in order to
try to overcome this major problem.
2.3 . Liquid Biopsy: CTCs (Circulating
Tumor Cells)
This project developed "CTC-derived xenografts” from patient’s CTCs as a
functional approach for assessing the patient’s pre-metastatic disease state.
We study the potential tropism of the tumor cells to specific microenvironment,
and explore the correlation between mutations in the primary tumor and
metastasis, in order to understand whether it is possible to predict
personalized anti-metastatic drug treatment based on the CTCs characteristic.
2.4. Patient
derived primary cultures.
In parallel to PDX models
for in-vivo studies, we establish an in-vitro platform of the patients tumor
cells grown in 3D manner (spheroids) in culture.
This complementary in-vitro system allow to study in more depth findings
derived from the in-vivo experiments (mechanism of actions , biomarkers etc),
or to serve as a screening platform for the best treatment that will be chosen
for validation in-vivo in the PDX models.
3. Collaborations
with academia and biomedical industry:
The PDX models combined with the corresponding frozen tissue, FFPE and
clinical data offer a valuable tool to perform advanced medical research, to try to develop newer anticancer therapies.
This resource are available for collaborative projects
with academia and biotech companies.
RA-292C, Lung