Improving neuroendocrine tumor treatments with mathematical modeling: lessons from other endocrine cancers.

Neuroendocrine tumors (NETs) occur sporadically or as part of rare endocrine tumor syndromes (RETSs) such as multiple endocrine neoplasia 1 and von Hippel-Lindau syndromes. Due to their relative rarity and lack of model systems, NETs and RETSs are difficult to study, hindering advancements in therapeutic development. Causal or mechanistic mathematical modeling is widely deployed in disease areas such as breast and prostate cancers, aiding the understanding of observations and streamlining and modeling efforts. Mathematical modeling, while not yet widely utilized in NET research, offers an opportunity to accelerate NET research and therapy development. To illustrate this, we highlight examples of how mathematical modeling associated with more common endocrine cancers has been successfully used in the preclinical, translational and clinical settings. We also provide a scope of the limited work that has been done in NETs and map how these techniques can be utilized in NET research to address specific outstanding challenges in the field. Finally, we include practical details such as hardware and data requirements, present advantages and disadvantages of various mathematical modeling approaches and discuss challenges of using mathematical modeling. Through a cross-disciplinary approach, we believe that many currently difficult problems can be made more tractable by applying mathematical modeling and that the field of rare diseases in endocrine oncology is well poised to take advantage of these techniques.