Dormancy in colorectal cancer: The functional core of resistance, metastasis, and relapse

Current treatments for colorectal cancer (CRC) can induce apparent disease remission; unfortunately, CRC eventually relapses in many patients. CRC recurrence has been associated with the presence of dormant cancer cells, which are difficult to detect and are maintained in a resilient state characterized by a low cell cycling rate. Dormant cancer cells evade immune surveillance, are not eliminated by conventional therapy, and employ specific metabolic programs enabling them to remain hidden for extended periods. Furthermore, the period elapsed since the onset of the disease, represents the opportunity where tumor has early spread to distant sites. Importantly, cellular dormancy and awakening are also involved in metastasis. This review explores the nuanced mechanisms involved in cellular dormancy, from remnant cancer cells of the primary tumor to metastatic cancer cells. The insights in this field hold promise to contribute clinical innovations for the improvement of predictive biomarkers or targeted therapies. Indeed, we address cell dormancy by unifying a set of concepts from modern oncology in light of the unique characteristics of CRC. Here, we discuss the immune system, metabolic imbalance, and drug tolerance; the major challenges that dormant cancer cells must overcome once awakened. This review reinforces the translational value of cellular dormancy as the foremost cause of recurrence and poor prognosis in colorectal cancer, with the aim of guiding the development of potential emergent treatments that can be combined with existing approaches such as chemotherapy and immunotherapy.