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Review
. 2022 Jan 10;40(1):26-35.
doi: 10.1016/j.ccell.2021.12.004. Epub 2021 Dec 23.

Functional precision oncology: Testing tumors with drugs to identify vulnerabilities and novel combinations

Anthony Letai  1 , Patrick Bhola  2 , Alana L Welm  3
Affiliations
Review

Functional precision oncology: Testing tumors with drugs to identify vulnerabilities and novel combinations

Anthony Letai et al. Cancer Cell. .

Abstract

Functional precision medicine is a strategy whereby live tumor cells from affected individuals are directly perturbed with drugs to provide immediately translatable, personalized information to guide therapy. The heterogeneity of human cancer has led to the realization that personalized approaches are needed to improve treatment outcomes. Precision oncology has traditionally used static features of the tumor to dictate which therapies should be used. Static features can include expression of key targets or genomic analysis of mutations to identify therapeutically targetable "drivers." Although a surprisingly small proportion of individuals derive clinical benefit from the static approach, functional precision medicine can provide additional information regarding tumor vulnerabilities. We discuss emerging technologies for functional precision medicine as well as limitations and challenges in using these assays in the clinical trials that will be necessary to determine whether functional precision medicine can improve outcomes and eventually become a standard tool in clinical oncology.

Keywords: Precision medicine; functional precision medicine; patient-derived models; precision oncology.

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Conflict of interest statement

Declaration of interests A.L.W. has received royalties from licenses of patient-derived xenograft or organoid models issued by the University of Utah. The University may issue new licenses in the future at its discretion, which may result in additional royalties. A.L. owns equity and serves on the scientific advisory boards of Zentalis Pharmaceuticals, Dialectic Therapeutics, Anji Onco, and Flash Therapeutics. A.L. has received royalties from licenses of BH3 profiling issued by the Dana-Faber Cancer Institute. The Institute may issue new licenses in the future at its discretion, which may result in additional royalties.

Figures

Figure 1.
Figure 1.. Models and readouts in functional precision medicine
Functional precision medicine directly exposes patient derived cancer cells (left panel) to therapeutics and measures drug response using various readouts (right panel). Patient derived material amenable to specific readouts are indicated by color codes in the right panel. The use of specific patient derived models in functional precision medicine has strengths and weaknesses outlined in the center panels
See this image and copyright information in PMC

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