Evolution of resistance is a common cause of cancer treatment failure and tumor progression in cancer dynamics. Standard therapy suggests to inoculate continuously the maximum tolerated dose after initiation. In this way the cells which are sensitive to treatment are eliminated quickly. However, there is a drawback. This procedure intensely selects for cells that are resistant to the treatment and eliminates the competition effects of alternative populations, resulting in rapid treatment failure and tumor progression. More recently, oncologists have understood that explicit incorporation of intratumoral dynamics in therapeutic trials may be very beneficial is rare. A number of recently developed treatment strategies have shown that some evolutionary principles can be used to prolong tumor control by inhibiting the emergence of treatment-resistant populations. Appropriately timed withdrawal of treatment can allow residual populations of sensitive cells to exploit their fitness advantage at the expense of the less-fit resistant phenotypes. While discontinuation of treatment allows tumor regrowth, the resistant subpopulation remains small so that retreatment with the same drug(s) remains effective. The goal of the thesis is to review the current frameworks in cancer ecology aiming at understanding models which can be used in non-standard, adaptive treatments. Prerequisites are standard mathematical tools from mathematical ecology and an open mind to new approaches.
Possible collaboration with S. Smye and P. Hillmen (Leeds, UK)
- Korolev, K.S., Xavier, J.B. and Gore, J., 2014. ‘‘Turning ecology and evolution against cancer’’. Nature Reviews Cancer, 14(5), p.371.
- Zhang, J., Cunningham, J.J., Brown, J.S. and Gatenby, R.A., 2017. ‘‘Integrating evolutionary dynamics into treatment of metastatic castrate-resistant prostate cancer’’. Nature communications, 8(1), p.1816.