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Tackling the tumor microenvironment - how can complex tumor models in vitro aid oncology drug development?
Megan C Cox1, Rita Mendes2,3, Kathleen N Halwachs1
1Oncology Discovery, AbbVie, United States of America, North Chicago, IL, USA.
Introduction:
Identifying effective cancer drugs remains an inefficient process. Drug efficacy in traditional preclinical cancer models translates poorly into therapy in the clinic. Implementation of preclinical models that incorporate the tumor microenvironment (TME) is needed to improve selection of active drugs prior to clinical trials.
Areas Covered:
Progression of cancer results from the behavior of cancer cells in concert with the host's histopathological background. Nonetheless, complex preclinical models with a relevant microenvironment have yet to become an integral part of drug development. This review discusses existing models and provides a synopsis of active areas of cancer drug development where implementation would be of value. Their contribution to finding therapeutics in immune oncology, angiogenesis, regulated cell death and targeting tumor fibroblasts as well as optimization of drug delivery, combination therapy, and biomarkers of efficacy is considered.
Expert Opinion:
Complex tumor models in vitro (CTMIVs) that mimic the organotypic architecture of neoplastic tumors have boosted research into TME influence on traditional cytoreductive chemotherapy as well as the detection of specific TME targets. Despite advances in technical prowess, CTMIVs can only address specific aspects of cancer pathophysiology.
Insights
Identifying effective cancer drugs is challenging due to poor translation from preclinical models. Incorporating the tumor microenvironment (TME) into these models is crucial for improving drug selection and clinical success.
Area of Science:
- Oncology
- Drug Discovery
- Preclinical Models
Background:
- Cancer progression is influenced by cancer cells and the tumor microenvironment (TME).
- Traditional preclinical cancer models poorly predict clinical drug efficacy.
- There is a need for advanced preclinical models that better mimic the TME.
Purpose of the Study:
- To review existing preclinical models that incorporate the TME.
- To discuss the application of TME-inclusive models in various cancer drug development areas.
- To highlight the importance of TME in improving cancer drug discovery.
Main Methods:
- Review of current literature on preclinical cancer models.
- Analysis of complex tumor models in vitro (CTMIVs).
- Synopsis of active areas in cancer drug development.
Main Results:
- CTMIVs offer insights into TME influence on chemotherapy and target detection.
- Despite advances, CTMIVs have limitations in fully capturing cancer pathophysiology.
- Implementation of TME-inclusive models is valuable across immune oncology, angiogenesis, and more.
Conclusions:
- Advanced preclinical models that mimic the TME are essential for efficient cancer drug development.
- Integrating TME into drug discovery pipelines can enhance the selection of effective cancer therapeutics.
- Further development and utilization of TME-inclusive models are needed to bridge the gap between preclinical findings and clinical outcomes.
