Hallmarks of Cancer Affected by the MIF Cytokine Family

SIMPLE SUMMARY: The aim of this review is to summarize the available information regarding the MIF family in cancer, comprising MIF and DDT. Both cytokines are highly expressed in cancer patients, and their functions are related to 9 out of 10 hallmarks of cancer, suggesting that this cytokine family may become an important target to improve existing cancer therapies. ABSTRACT: New diagnostic methods and treatments have significantly decreased the mortality rates of cancer patients, but further improvements are warranted based on the identification of novel tumor-promoting molecules that can serve as therapeutic targets. The macrophage migration inhibitory factor (MIF) family of cytokines, comprising MIF and DDT (also known as MIF2), are overexpressed in almost all cancer types, and their high expressions are related to a worse prognosis for the patients. MIF is involved in 9 of the 10 hallmarks of cancer, and its inhibition by antibodies, nanobodies, or small synthetic molecules has shown promising results. Even though DDT is also proposed to be involved in several of the hallmarks of cancer, the available information about its pro-tumoral role and mechanism of action is more limited. Here, we provide an overview of the involvement of both MIF and DDT in cancer, and we propose that blocking both cytokines is needed to obtain the maximum anti-tumor response.