Aravive-S6 is a novel therapeutic candidate
under development by Aravive Biologics, Inc. It is designed to selectively inhibit the AXL-signaling
pathway which acts as a "survival switch" that scientists believe
promotes tumor growth and metastasis, and resistance to common
New preclinical research published online today in Nature Communications
suggests a potential role for Aravive-S6 to increase tumor
sensitivity to radiation therapy and check-point immuno-oncology agents.
‘Aravive-S6 increases tumor sensitivity to radiation therapy and check-point immuno-oncology agents.’
The new research adds to evidence that AXL
over-expression also results in tumor unresponsiveness to radiation and
check-point inhibitors, and further shows that inhibiting AXL signaling
elicits an anti-tumor immune response and sensitizes tumors to radiation
and other anticancer therapies including PD-1 inhibitors and other
The publication, entitled "Reprogramming the Immunologic
Microenvironment through Radiation and Targeting AXL," was authored by
Amato J. Giaccia, scientific founder and acting chief scientific
officer of Aravive Biologics, and his research collaborators at Stanford
Dr. Giaccia commented, "Checkpoint inhibitors have demonstrated
dramatic anti-tumor responses as single agents in about 10-30% of
patients, and there is increasing clinical evidence that these agents
may achieve further anti-cancer synergies in combination with radiation
therapy. Unfortunately, some tumors remain resistant to these
approaches, and the aim of our research was to better understand the
mechanisms underlying such resistance."
The researchers analyzed genetic, tumor micro-environmental, and
immunologic factors in tumors derived from a transgenic model of breast
cancer. They identified two tumors with similar growth characteristics
but different responses to radiation therapy.
Profiling the tumors
revealed that the AXL receptor was over-expressed in the unresponsive
tumors, and that knocking out AXL resulted in slower tumor growth,
increased tumor sensitivity to radiation, and an anti-tumor CD8+ T-cell
response that was improved with combination checkpoint immunotherapy.
"This research further increases our understanding of AXL as a key
anticancer target, whose selective inhibition can overcome tumor
resistance and increase the efficacy of a variety of anticancer agents,
including radiation therapy and immuno-oncology approaches," said Dr.
"Inhibiting AXL enhances MHC Class 1 expression, and recruits
T-cells into the tumor by reversing the mesenchymal phenotype of the
tumor to an epithelial phenotype. While the radiation and
PD1/CTLA-resistant tumors were sensitive to AXL inhibition alone, the
combination of anti-AXL and checkpoint inhibitors seems to work better
in eliciting an anti-tumor response."
"Recently published preclinical research has shown Aravive-S6, our
novel anti-AXL inhibitor, to exhibit potent preclinical activity against
AML and advanced ovarian, pancreatic and breast tumors, both as a
single agent and in synergy with cytotoxic drugs," said Ray Tabibiazar,
President and Chief Executive Officer of Aravive Biologics.
new research suggests that Aravive-S6 may also be a useful agent in
combination with checkpoint inhibitors such as PD1, PDL1 or CTLA4
inhibitors. We look forward to continuing our development of
Aravive-S6, with a goal of filing an IND by the end of 2017."