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Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms

Published on: December 9, 2015

Materials-driven approaches to understand extrinsic drug resistance in cancer

Justin R Pritchard¹, Michael J Lee², Shelly R Peyton³

¹Department of Biomedical Engineering, Pennsylvania State University, State College PA, USA.

|April 21, 2022

Abstract:

Metastatic cancer has a poor prognosis, because it is broadly disseminated and associated with both intrinsic and acquired drug resistance. Critical unmet needs in effectively killing drug resistant cancer cells include overcoming the drug desensitization characteristics of some metastatic cancers/lesions, and tailoring therapeutic regimens to both the tumor microenvironment and the genetic profiles of the resident cancer cells. Bioengineers and materials scientists are developing technologies to determine how metastatic sites exclude therapies, and how extracellular factors (including cells, proteins, metabolites, extracellular matrix, and abiotic factors) at metastatic sites significantly affect drug pharmacodynamics. Two looming challenges are determining which feature, or combination of features, from the tumor microenvironment drive drug resistance, and what the relative impact is of extracellular signals vs. intrinsic cell genetics in determining drug response. Sophisticated systems biology tools that can de-convolve a crowded network of signals and responses, as well as controllable microenvironments capable of providing discrete and tunable extracellular cues can help us begin to interrogate the high dimensional interactions governing drug resistance in patients.

Insights

Overcoming drug resistance in metastatic cancer requires understanding how the tumor microenvironment and genetics impact therapy. New bioengineering tools are being developed to address these challenges in patient treatment.

Area of Science:

Biomedical Engineering
Materials Science
Cancer Biology

Background:

Metastatic cancer presents a poor prognosis due to widespread dissemination and drug resistance.
Current treatments struggle to overcome drug desensitization and tailor therapies to individual tumor characteristics.
Understanding the interplay between the tumor microenvironment and cancer cell genetics is crucial for effective treatment.

Purpose of the Study:

To explore the challenges in overcoming drug resistance in metastatic cancer.
To investigate the role of the tumor microenvironment and genetic profiles in therapeutic response.
To highlight the development of new technologies for analyzing drug resistance mechanisms.

Main Methods:

Developing advanced bioengineering and materials science technologies.
Investigating how metastatic sites affect drug delivery and efficacy.
Utilizing sophisticated systems biology tools and controllable microenvironments.

Main Results:

Identifying factors within the tumor microenvironment that contribute to drug resistance.
Assessing the impact of extracellular signals versus intrinsic cell genetics on drug response.
Gaining insights into the complex interactions governing drug resistance in patients.

Conclusions:

Addressing drug resistance in metastatic cancer necessitates a multi-faceted approach.
Advanced technological tools are essential for dissecting the complex mechanisms of drug resistance.
Tailoring therapies based on tumor microenvironment and genetic profiles holds promise for improved patient outcomes.

Read full analysis

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