Mathematical Models of Cancer: When to Predict Novel Therapies, and When Not to

Abstract

The number of publications on mathematical modeling of cancer is growing at an exponential rate, according to PubMed records, provided by the US National Library of Medicine and the National Institutes of Health. Seminal papers have initiated and promoted mathematical modeling of cancer and have helped define the field of mathematical oncology (Norton and Simon in J Natl Cancer Inst 58:1735-1741, 1977; Norton in Can Res 48:7067-7071, 1988; Hahnfeldt et al. in Can Res 59:4770-4775, 1999; Anderson et al. in Comput Math Methods Med 2:129-154, 2000. https://doi.org/10.1080/10273660008833042 ; Michor et al. in Nature 435:1267-1270, 2005. https://doi.org/10.1038/nature03669 ; Anderson et al. in Cell 127:905-915, 2006. https://doi.org/10.1016/j.cell.2006.09.042 ; Benzekry et al. in PLoS Comput Biol 10:e1003800, 2014. https://doi.org/10.1371/journal.pcbi.1003800 ). Following the introduction of undergraduate and graduate programs in mathematical biology, we have begun to see curricula developing with specific and exclusive focus on mathematical oncology. In 2018, 218 articles on mathematical modeling of cancer were published in various journals, including not only traditional modeling journals like the Bulletin of Mathematical Biology and the Journal of Theoretical Biology, but also publications in renowned science, biology, and cancer journals with tremendous impact in the cancer field (Cell, Cancer Research, Clinical Cancer Research, Cancer Discovery, Scientific Reports, PNAS, PLoS Biology, Nature Communications, eLife, etc). This shows the breadth of cancer models that are being developed for multiple purposes. While some models are phenomenological in nature following a bottom-up approach, other models are more top-down data-driven. Here, we discuss the emerging trend in mathematical oncology publications to predict novel, optimal, sometimes even patient-specific treatments, and propose a convention when to use a model to predict novel treatments and, probably more importantly, when not to.

Keywords: Mathematical oncology; Optimization; Parameter estimation; Treatment prediction.

Fig. 1

PubMed query for “Mathematical model” AND (“cancer” OR “tumor”), accessed 3/1/19. The trend line indicates an exponential increase in number of mathematical oncology publications since 1968 (Color figure online)

Fig. 2

Proposed pipeline for predicting novel, potentially optimal therapy. Dashed arrows mark commonly used shortcuts to predictions that should be avoided in translational models to predict novel treatments (Color figure online)