Modelling the Tumour Microenvironment, but What Exactly Do We Mean by "Model"?

Abstract

The Oxford English Dictionary includes 17 definitions for the word "model" as a noun and another 11 as a verb. Therefore, context is necessary to understand the meaning of the word model. For instance, "model railways" refer to replicas of railways and trains at a smaller scale and a "model student" refers to an exemplary individual. In some cases, a specific context, like cancer research, may not be sufficient to provide one specific meaning for model. Even if the context is narrowed, specifically, to research related to the tumour microenvironment, "model" can be understood in a wide variety of ways, from an animal model to a mathematical expression. This paper presents a review of different "models" of the tumour microenvironment, as grouped by different definitions of the word into four categories: model organisms, in vitro models, mathematical models and computational models. Then, the frequencies of different meanings of the word "model" related to the tumour microenvironment are measured from numbers of entries in the MEDLINE database of the United States National Library of Medicine at the National Institutes of Health. The frequencies of the main components of the microenvironment and the organ-related cancers modelled are also assessed quantitatively with specific keywords. Whilst animal models, particularly xenografts and mouse models, are the most commonly used "models", the number of these entries has been slowly decreasing. Mathematical models, as well as prognostic and risk models, follow in frequency, and these have been growing in use.

Keywords: computational model; in vitro model; in vivo model; mathematical model; model organism; tumour microenvironment.

Figure 1

Numbers of entries indexed in PubMed for individual queries. Each query concatenated the individual keyword with the date range of (2000:2023[dp]) and restrictions corresponding to tumour microenvironment (((“tumor microenvironment”) OR (“tumour microenvironment”)) OR (“cancer microenvironment”)). Colours are allocated for organism (red), mathematical (blue), in vitro (green) and computational (brown) models for visualisation purposes. The legend in the top right indicates the aggregates per group.

Figure 2

Numbers of entries indexed in PubMed for individual queries per year of publication aggregated by the four groups. Each coloured ribbon corresponds to the sum of the keywords of each group, and the year increases as indicated by the axes on the right. It should be noticed how some techniques are more established (i.e., organism model) whilst others are more recent (computational model).

Figure 3

Numbers of entries indexed in PubMed for individual queries. In this case, the query included a keyword, e.g., angiogenesis, and the word “model”. It should be noted that the vertical axis is logarithmic.

Figure 4

Relative numbers of entries indexed in PubMed for individual queries. Each ratio represents the entries of one keyword to the total number of entries of all the keywords per year. (a) Keywords that showed the largest increases. (b) Keywords that showed increases but at a smaller scale (notice the differences in the vertical axes). (c) Keywords that showed decreased. (d) Keywords that remained relatively stable.

Figure 5

Numbers of entries indexed in PubMed for individual queries. In this case, the query included organ-specific keywords.

Figure 6

Numbers of entries indexed in PubMed for queries with pairs of keywords for models and organs. Each 3D bar corresponds to the number of entries in PubMed of a specific pair of keywords. The colours correspond to those of Figure 1.

Figure 7

Numbers of entries indexed in PubMed for queries with pairs of keywords for models and organs for cases with the highest results from Figure 5.