Conceptualizing cancer drugs as classifiers

Patrick Nathan Lawlor, Tomer Kalisky, Robert Rosner, Marsha Rich Rosner, Konrad Paul Kording

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Cancer and healthy cells have distinct distributions of molecular properties and thus respond differently to drugs. Cancer drugs ideally kill cancer cells while limiting harm to healthy cells. However, the inherent variance among cells in both cancer and healthy cell populations increases the difficulty of selective drug action. Here we formalize a classification framework based on the idea that an ideal cancer drug should maximally discriminate between cancer and healthy cells. More specifically, this discrimination should be performed on the basis of measurable cell markers. We divide the problem into three parts which we explore with examples. First, molecular markers should discriminate cancer cells from healthy cells at the single-cell level. Second, the effects of drugs should be statistically predicted by these molecular markers. Third, drugs should be optimized for classification performance. We find that expression levels of a handful of genes suffice to discriminate well between individual cells in cancer and healthy tissue. We also find that gene expression predicts the efficacy of some cancer drugs, suggesting that these cancer drugs act as suboptimal classifiers using gene profiles. Finally, we formulate a framework that defines an optimal drug, and predicts drug cocktails that may target cancer more accurately than the individual drugs alone. Conceptualizing cancer drugs as solving a discrimination problem in the high-dimensional space of molecular markers promises to inform the design of new cancer drugs and drug cocktails.

Original languageEnglish
Article numbere106444
JournalPLoS ONE
Volume9
Issue number9
DOIs
StatePublished - 23 Sep 2014

Bibliographical note

Publisher Copyright:
© 2014 Lawlor et al.

Funding

FundersFunder number
National Institutes of Health5P01NS044393
National Institute of Neurological Disorders and StrokeR01NS063399

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