Towards multi-drug adaptive therapy
Jeffrey West, Li You, Joel Brown, Paul K. Newton, and Alexander R. A. Anderson
Received Date: 6th December 18
A new ecologically inspired paradigm in cancer treatment known as "adaptive therapy" capitalizes on competitive interactions between drug-sensitive and drug-resistant subclones. The goal of adaptive therapy is to maintain a controllable stable tumor burden by allowing a significant population of treatment sensitive cells to survive. These, in turn, suppress proliferation of the less fit resistant populations. However, there remain several open challenges in designing adaptive therapies, particularly in extending these therapeutic concepts to multiple treatments. We present a cancer treatment case study (metastatic castrate resistant prostate cancer) as a point of departure to illustrate three novel concepts to aid the design of multi-drug adaptive therapies. First, frequency-dependent ``cycles” of tumor evolution can trap tumor evolution in a periodic, controllable loop. Second, the availability and selection of treatments may limit the evolutionary ``search space" reachable by the tumor. Third, the velocity of evolution significantly influences the optimal timing of drug sequences.
Read in full at bioRxiv.
This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.