Cancer-associated fibroblasts as a potential target in oncology therapy

Abstract

Tumors make up a complex environment that consists of intensive proliferating cancer cells surrounded by normal cells. Fibroblasts recruited by cancer termed CAFs, are one of the major cell groups within the reactive stroma of the most common tumors. Because of the crosstalk between quiescent fibroblasts and cancer cells, fibroblasts undergo phenotypic transition and acquire new functions that have been "forced by a tumor". CAFs affect the development of the drug resistance and cancer progression as they are involved in the growth of cancers, neoangiogenesis, immune evasion and metastatic colonisation in distant organs. Fibroblast-directed therapy offers the opportunity to prevent initiation, progression and metastasis of many invasive tumors. The current studies on CAF-based therapy focus on two strategies. The first strategy leads to the elimination of CAFs and the neutralization of their released factors and the second aims at reverting the CAF-phenotype to a "normal" fibroblast-phenotype. Although the results of preclinical studies conducted on cell cultures and animal models indicate that therapy aimed at reversion or inhibition CAFs function seem to be a promising therapeutic target, available clinical studies have not yet confirmed this. Nevertheless, it is necessary to underline that until now CAF-based therapy has been used in patients with advanced cancer and there is no clinical study using such therapy in the early stage of cancer. The available data also indicates that CAF-based therapy could be used in combination with common anticancer drugs to increase their effectiveness. Therefore, further studies on the usefulness of the proposed CAF-based therapy are needed.