Cyclotherapy: opening a therapeutic window in cancer treatment

Abstract

Cyclotherapy is a promising endeavor to improve cancer treatment by tackling the dose-limiting side effects of chemotherapy, especially for cancers harboring mutations in the TP53 tumor suppressor. In this particular context, pretreatment with a p53 activator halts proliferation in healthy tissue, while leaving the p53-deficient tumor susceptible to conventional chemotherapy.

Figure 1. The cyclotherapy concept illustrated for patients with p53-mutant tumors

Pre-incubation with a small-molecule p53 activator selectively induces cell arrest in normal cells, thereby protecting them from subsequent exposure to a classic S or M phase-specific cytotoxic drug without compromising the anticancer efficacy of the treatment.

Figure 2. Effective chemoprotection of normal cells from nuclear aberrations caused by a tubulin poison

Human normal dermal fibroblasts were (A) left untreated, (B) treated with 40 nM vinorelbine as a sole agent for 48 h or (C) pre-incubated with 3 μM tenovin-6 prior to exposure to vinorelbine. Cells were then left to recover for several days in fresh medium and stained with Giemsa.