Adaptive therapy achieves long-term control of chemotherapy resistance in high grade ovarian cancer

Drug resistance leads to poor outcomes in metastatic cancer. Adaptive Therapy (AT) seeks to exploit fitness costs in drug-resistant cells by reducing doses to allow fitter, drug-sensitive cells to regrow and suppress resistant populations. Here, we demonstrate that chemotherapy-resistant ovarian cancer cells incur fitness costs in low-resource conditions, resulting in selective decline and apoptosis of resistant cells. Carboplatin AT induced fluctuations in sensitive and resistant populations in vitro and significantly extended survival in tumour-bearing mice. In longitudinal patient samples, we inferred resistant population size using liquidCNA (LiqCNA) from copy number alterations, and this correlated strongly with disease burden. These findings underpin a multicentre phase 2 randomised controlled trial (ACTOv) to evaluate AT in ovarian cancer.

Helen Hockings, Eszter Lakatos, Weini Huang, Maximilian Mossner, Mohammed Ateeb Khan, Stephen Metcalf, Francesco Nicolini, Kane Smith, Ann-Marie Baker, Trevor A Graham, Michelle Lockley