Research progress on therapeutic targeting of quiescent cancer cells

Abstract

Cellular quiescence (G0) is a sleep-like cellular state that allows cells to maintain the ability to re-enter and exit the proliferative cycle. Quiescent cancer cells are considered a therapeutic challenge since they are often resistant to conventional chemoradiotherapy resulting in disease progression and relapse. To date, the majority of published studies have focused on identifying molecules that target proliferating tumor cells while limited information is available on methods to target quiescent cancer cells. This review provides a summary of the relevant molecular mechanisms underlying quiescence maintenance and pharmacological interventions aimed at either eliminating this cancer cell subpopulation or indefinitely maintaining the quiescence state. Furthermore, the irradiation responses of quiescent cancer cells, in particular, the influence of manipulating intratumor hypoxia and radiation properties on radiosensitivity, are discussed. The main aim of this article is to provide a theoretical basis for the effective targeted killing of dormant tumor cells. ARTICLE HISTORY

High-throughput screening reveals higher synergistic effect of MEK inhibitor combinations in colon cancer spheroids

“…In contrast to 2D-cultured cells, where the larger part of the cell population is actively proliferating, 3D cultures are considerably more heterogeneous with respect to the proliferative capacity and have, unlike cells cultured in 2D, been found to contain a non-proliferating quiescent or hypoxic cell population similar to that of tumours in vivo 8 . Clinically, quiescent tumour cell populations constitute a major treatment hurdle, as the quiescent phenotype frequently is associated with resistance to standard therapies 11,12 . Monitoring the effect of drugs considering also non-proliferating cells may therefore be of great significance in order to increase the bench-to-bed translational efficiency.…”

Harnessing the targeting potential of differential radiobiological effects of photon versus particle radiation for cancer treatment

“…Cellular quiescence is a reversible cellular state that allows cells to re-enter and exit the proliferative cycle (J. Zhang et al, 2019).…”

“…Cellular quiescence is a reversible cellular state that allows cells to re‐enter and exit the proliferative cycle (J. Zhang et al, 2019). It is believed that quiescent tumour cells are more resistant to IR, due to their large hypoxic fraction and greater repair abilities, when compared with cycling tumour cells (Masunaga et al, 2008; Pei et al, 2017).…”

PP2A and tumor radiotherapy

“…Understanding the mechanistic basis for tumor cell chemoresistance and radioresistance is thus vital. Interestingly, recent research evidence suggests that radiosensitization can be achieved by accelerating cell cycle progression in quiescent cells such that they become proliferative [ 10 , 11 ]. Inhibiting proteins such as PP2A can drive quiescent tumor cells to enter mitosis, in turn potentially increasing tumor cell sensitivity to treatment [ 12 , 13 ].…”