Periodic Reporting for period 1 - PHRD (The development of Personalised Host Response Diagnostic kit)
Reporting period: 2017-04-01 to 2018-09-30
One of the major obstacles in clinical oncology is that tumors often develop resistance to therapy even when an initial tumor response to treatment is observed. Many studies have focused on the contribution of mutations and genetic aberrations in the tumor cells which promote drug resistance and can explain tumor re-growth. However, we have demonstrated that the host, in response to therapy, generates pro-tumorigenic and pro-metastatic effects which in turn contribute to tumor re-growth, and therefore negate the anti-tumor activity of the drug. For example, in preclinical studies we have demonstrated that tumor cells become aggressive when they are co-cultured with blood product obtained from mice that were pre-treated with paclitaxel chemotherapy when compared to blood product from control mice. These tumor cell aggressive properties were also documented in vivo in mice. Specifically, mice that were ‘preconditioned’ with paclitaxel chemotherapy and subsequently injected with tumor cells succumbed to metastasis earlier than control mice. This relatively new phenomenon has made a paradigm shift in understanding cancer progression and resistance to therapy. In this project we have analyzed the host-mediated responses to chemotherapy and immunotherapy in human and mouse. We discovered a novel set of host-driven tumor resistance or progression factors which limit effectiveness of current treatments. Such factors consist of circulating cytokines, chemokines, and growth factors, each of which is associated with different hallmarks of cancer. Therefore, the detection of these factors in the blood of cancer patients undergoing therapy can potentially be used to predict therapy outcome. The work has led to the foundation of a start-up company which uses the know-how to develop a kit for personalized therapy. The goal is to help oncologists with a decision making regarding the beneficial therapeutic approach for cancer patients in a personalized manner.