Abstract
Cancer is a disease characterized by its high morbidity and mortality, mainly due to its metastatic ability. Metastasis is a multi-step process beginning with detachment of tumor cells from the primary tumor and leading ultimately to the establishment of a new tumoral site. This cascade includes intravascular migration of tumor cells either individually or collectively and the expansion of cancer cells at metastatic sites that is dependent on certain conditions such as an immunosuppressive environment. In this paper, blockers of tumor cell migration and suppressors of immunotolerance at metastatic sites are reviewed as an illustration of early and later phases intervention, respectively. A combination of these two therapeutics will be advocated based on the proposition of correlation between the pattern of tumor cell migration and the mechanism of immunotolerance induction. By extension, the ''delayed complementarity'' will be introduced as an approach to formulate new anticancer drug combinations.
Highlights
BackgroundMetastasis is the ensemble of steps that some tumor cells follow to migrate from a tumor site to another distant one [1]
This cascade includes intravascular migration of tumor cells either individually or collectively and the expansion of cancer cells at metastatic sites that is dependent on certain conditions such as an immunosuppressive environment
Blockers of tumor cell migration and suppressors of immunotolerance at metastatic sites are reviewed as an illustration of early and later phases intervention, respectively
Summary
Metastasis is the ensemble of steps that some tumor cells follow to migrate from a tumor site to another distant one [1]. An example extensively tested in experimental models is the association between MDSC-targeting drugs and immune checkpoint inhibitors This combo had shown encouraging outcomes and is adopted by many ongoing clinical trials [31]. That means that tumor cells following a pathway that is not blocked by the first inhibitor are expected to depend at the later phase on a mechanism repressible by the second agent Can this approach be used to realize a combination between tumor cells migration inhibitors and immunotolerance suppressors? The association of tumor cell migration inhibitors and immunotolerance blockers is targeting mainly the metastatic process If it demonstrates satisfactory results, therapeutic interventions targeting the primary tumoral site should be considered. This illustrated combination should be introduced at an earlier phase of cancer progression, as it is acting on the prevention of metastatic site formation
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