Toward improved in vitro models of human cancer

Abstract

Cancer is a leading cause of death across the world and continues to increase in incidence. Despite years of research, multiple tumors (e.g., glioblastoma, pancreatic cancer) still have limited treatment options in the clinic. Additionally, the attrition rate and cost of drug development have continued to increase. This trend is partly explained by the poor predictive power of traditional in vitro tools and animal models. Moreover, multiple studies have highlighted that cell culture in traditional Petri dishes commonly fail to predict drug sensitivity. Conversely, animal models present differences in tumor biology compared with human pathologies, explaining why promising therapies tested in animal models often fail when tested in humans. The surging complexity of patient management with the advent of cancer vaccines, immunotherapy, and precision medicine demands more robust and patient-specific tools to better inform our understanding and treatment of human cancer. Advances in stem cell biology, microfluidics, and cell culture have led to the development of sophisticated bioengineered microscale organotypic models (BMOMs) that could fill this gap. In this Perspective, we discuss the advantages and limitations of patient-specific BMOMs to improve our understanding of cancer and how these tools can help to confer insight into predicting patient response to therapy.

FIG. 1.

Schematic representation of a comparison among bioengineered microscale organotypic models (BMOMs), in vitro and in vivo models. BMOMs are a balanced middle ground between the advantages of in vitro models (purple) and the advantages of in vivo models (green). Further, the leverage of microscale technologies comes with advantages over both in vitro and in vivo models (red).

FIG. 2.

The precision medicine “puzzle.” We envision that precision medicine will rely on the convergence of four main pillars: patients, animal models, organotypic microscale models, and computational models. Interdisciplinary and collaborative work will be necessary to achieve this goal. Further, active collaboration of universities, industry, patient advocate groups and the government remain to be pieced into this concerted effort.