The importance of developing therapies targeting the biological spectrum of metastatic disease

Abstract

Great progress has been made in cancer therapeutics. However, metastasis remains the predominant cause of death from cancer. Importantly, metastasis can manifest many years after initial treatment of the primary cancer. This is because cancer cells can remain dormant before forming symptomatic metastasis. An important question is whether metastasis research should focus on the early treatment of metastases, before they are clinically evident ("overt"), or on developing treatments to stop overt metastasis (stage IV cancer). In this commentary we want to clarify why it is important that all avenues of treatment for stage IV patients are developed. Indeed, future treatments are expected to go beyond the mere shrinkage of overt metastases and will include strategies that prevent disseminated tumor cells from emerging from dormancy.

Keywords: Cancer dormancy; Liquid biopsy; Metastasis; Minimal residual disease; Stage IV cancer.

Figure 1:. Side-by-side depictions of treatment scenarios for advanced cancer to highlight the benefit of stopping the emergence of overt metastasis from dormant disseminated cancer.

A) A treatment scenario in which the dormant disseminated cancer is not considered. B) A treatment scenario where, in conjunction with conventional therapy, additional treatment targeting dormant disease significantly delays (a) or prevents entirely (b) the emergence of overt metastasis years and even decades after treatment for the primary tumor was deemed successful; scenario b could be achieve by maintaining dormancy or by eradicating the dormant disseminated tumor cells. Also treatment of overt metastasis could include therapies to kill dormant disseminated tumor cells and thus stop not only proliferative, but also non-proliferative cells in metastatic organs.