Evolution underlies both the development of humankind as well as the greatest challenges to human health. Across the tree of life, cancer and infectious viruses, prokaryotes, and eukaryotes exist within complex competitive landscapes that can promote or inhibit disease progression and therapeutic resistance. The amazing diversity of heterogenous cell populations raises existential questions about how to combat drug resistance evolution. A conventional approach to this problem is to attempt to reverse engineer evolving biological systems. I.e., after a selection has occurred, we isolate resistant cells, attempt to determine what caused drug resistance and treat the resistant state. However, this strategy results in a “resistance treadmill” whereby resistance evolution occurs, new drugs combat drug resistance and then resistance re-emerges – a process that occurs until we run out of effective agents. We propose to employ a forward engineering approach that seeks to “build to understand” as well as control drug resistance.
Drug resistance can be both intrinsic and acquired. In intrinsic drug resistance cells are insensitive to treatment before a therapeutic is ever applied. In a patient this means that a drug is given, and the disease doesn’t respond. In acquired drug resistance treatment with a drug selects for drug resistance to grow out. In this case a patient initially gets better, but the resistant eventually comes back.