Researchers offer new treatment protocol for advanced head and neck
cancer

Date:
March 28, 2022
Source:
Ben-Gurion University of the Negev
Summary:
The current treatment of patients diagnosed with advanced or
metastatic head and neck cancer (HNC) is ineffective. Researchers
have investigated and validated a potential treatment combination
against the aggressive disease driven by hyper-activation of a
specific signaling pathway, which is found in over 40 percent of
HNC patients.



FULL STORY ==========================================================================
The current treatment of patients diagnosed with advanced or metastatic
head and neck cancer (HNC) is ineffective. Ben-Gurion University of
the Negev researchers, along with their international colleagues, have investigated and validated a potential treatment combination against the aggressive disease driven by hyper-activation of a specific signaling
pathway, which is found in over 40% of HNC patients.


========================================================================== Their findings were just published in the Journal for ImmunoTherapy
of Cancer.

Specifically, the authors showed in pre-clinical HNC models that treating tumor-bearing mice with a therapy that blocks this signaling pathway, sensitizes tumors to the immunotherapy of anti-PD1, resulting in the disappearance of tumors after the therapy combination. This effective
treatment was validated in four HNC cancer models, and most mice were
cured with no recurrent disease. Together with Dr. Pierre Saintygn from
Lyon the authors also validated some of the findings in HNC patients.

The research was led by PhD student Manu Prasad in the laboratory of Prof.

Moshe Elkabets in the Faculty of Health Sciences at Ben-Gurion University
of the Negev.

"Our unique ability to generate pre-clinical HNC models and to
investigate new treatment and treatment combinations provides hope
for HNC patients. We sincerely hope that oncologists will test this
treatment combination in HNC patients, as improving immunotherapy
efficacy is crucial for prolonging the survival of cancer patients,"
says Prof. Elkabets.

The authors also showed for the first time in mice bearing HNC that
the treatment should be given sequentially. They found that a short
treatment with trametinib is sufficient to sensitize anti-PD-1 resistant tumors. This sensitization happens because trametinib treatment,
on the one hand, inhibits tumor cell proliferation and, on the other
hand, down-regulates the expression of an immunosuppressive factor
that determines the propagation of immunosuppressive cells in the
tumor site. This effect enables cytotoxic white blood cells to reach
the tumor site, and together with anti-PD1, can kill the tumor cells efficiently. However, when mice were treated with prolonged trametinib treatment, tumors failed to respond to immunotherapy.

The study was conducted by national and international groups from Soroka University Medical Center and Barzilai Medical Centers, Memorial Sloan Kettering, and Heidelberg Hospital.

This study was supported by the Cooperational Research Program of the Foundation Deutsches Krebsforschungszentrum, Heidelberg, with the Ministry
of Science, Technology & Space (DKFZ-MOST #001192), the Israel Cancer
Research Fund (ICRF 17-1693-RCDA), the United States -- Israel Binational Science Foundation (BSF, 2017323), NSFC Israel-China project (#3409/20)
and the Israel Science Foundation (ISF) Grant no. 700/16 and 302/21.


========================================================================== Story Source: Materials provided by
Ben-Gurion_University_of_the_Negev. Note: Content may be edited for
style and length.


========================================================================== Journal Reference:
1. Manu Prasad, Jonathan Zorea, Sankar Jagadeeshan, Avital B Shnerb,
Sooraj
Mathukkada, Jebrane Bouaoud, Lucas Michon, Ofra Novoplansky,
Mai Badarni, Limor Cohen, Ksenia M Yegodayev, Sapir Tzadok, Barak
Rotblat, Libor Brezina, Andreas Mock, Andy Karabajakian, Je'ro^me
Fayette, Idan Cohen, Tomer Cooks, Irit Allon, Orr Dimitstein,
Benzion Joshua, Dexin Kong, Elena Voronov, Maurizio Scaltriti,
Yaron Carmi, Cristina Conde-Lopez, Jochen Hess, Ina Kurth, Luc G
T Morris, Pierre Saintigny, Moshe Elkabets.

MEK1/2 inhibition transiently alters the tumor immune
microenvironment to enhance immunotherapy efficacy against head
and neck cancer. Journal for ImmunoTherapy of Cancer, 2022; 10
(3): e003917 DOI: 10.1136/jitc-2021- 003917 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/03/220328111810.htm

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