University of Ioannina, PC 45110, Greece
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Basic Biomedical Sciences

"Combination of metronomic chemotherapy and immunotherapy - Theoretical and experimental approach"

Abstract

Oncology has benefited from an increasingly growing number of groundbreaking innovations over the last decade. Immune checkpoint inhibitors, anti-angiogenics and targeted therapies have already entered the clinic with various level of success. On the other hand, conventional cytotoxic chemotherapy appears to have reached a plateau in efficacy for most major solid cancers. Alternative dosing schedules such as metronomic regimens, based upon the repeated and regular administration of low doses of chemotherapeutic drugs, have emerged as possible strategies to improve response rates while reducing toxicities. The recent changes in paradigm in the way we theorize cancer biology and evolution, metastatic spreading and tumor ecology, alongside the recent advances in the field of immunotherapy, have considerably strengthened the interest for these alternative approaches. The evidence of the multi-targeted nature of Metronomic chemotherapy and the possible combination with repositioned drugs, targeted therapies and immunotherapy have paved the way for the expansion of personalized precision chemotherapy. Furthermore, cancer immunotherapies are rapidly changing traditional treatment paradigms and expanding the therapeutic landscape for cancer patients. However, despite the current success of these therapies, not all patients respond to immunotherapy and even those that do, often experience toxicities.

A promising approach is to block the immunosuppressive mechanisms, such as CTLA-4 and the PD-1/PD-L1 axis, to augment the function of endogenous antitumor T cells, which can deliver a robust and effective clinical response. One of the main objectives of Metronomic chemotherapy is to tilt the immunological balance from immunosuppression to immunostimulation and so Metronomic chemotherapy has already been combined with several types of immunotherapy, with variant responses. Nevertheless, the position of Metronomic therapy alone or combined with immunotherapy in cancer fight, should to be further explored.

ILIA Helen