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Host molecular and cellular responses to anti-cancer drug treatment as a potential biomarker for treatment outcome

Final Report Summary - HOSTRESPONSE (Host molecular and cellular responses to anti-cancer drug treatment as a potential biomarker for treatment outcome.)

Chemotherapy, radiation, and surgery are the conventional treatment modalities for cancer. Although treatment benefit is usually achieved, cancer may sometimes relapse. Over the years, cancer researchers attempted to uncover possible mechanisms of cancer resistance to therapy. While the majority have searched for the selectivity and flexibility of cancer cells to escape therapy, our laboratory has focused on changes occurred in the tumor microenvironment which can support its growth. We found that almost any type of anti-cancer treatment including chemotherapy, radiation, surgery and targeted drugs can induce host molecular and cellular effects which, in turn, can lead to tumor outgrowth and relapse despite an initial successful therapy outcome. Tumor relapse due to host effects is attributed to angiogenesis, tumor cell dissemination from the primary tumors and seeding at metastatic sites. Various bone marrow derived cells participate in this process, and many different factors are secreted from host cells in response to the therapy which then lead to tumor relapse and even resistance to therapy. The changes in the tumor microenvironment following therapy have not been investigated thoroughly, as tools to track such changes are not widely spread. In my laboratory we focused on studying these specific host effects in response to different types of therapy and their possible clinical implications. We will uncover the changes occurred in the host and at the tumor, and identify whether host pro-tumorigenic and pro-metastatic effects take place following different type of therapies. Our results will pave the way for new treatment modalities for cancer which can block the host response effects using either new developed drugs, or repurpose drugs that are already in the market but for other indications. In addition, our results will further improve personalized medicine that is based on individual host response in order to predict the therapy outcome.