A Synergetic Screening Approach with Companion Effector for Combination Therapy

Application to Retinoblastoma

Jeni P. Mahida, Christophe Antczak, Daniel DeCarlo, Kathryn G. Champ, Jasmine H. Francis, Brian Marr, Arthur S. Polans, Daniel Albert, David H. Abramson, Hakim Djaballah

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

For many cancers, the lack of potency and the toxicity of current drugs limits the dose achievable in patients and the efficacy of treatment. Among them, retinoblastoma is a rare cancer of the eye for which better chemotherapeutic options are needed. Combination therapy is a compelling approach to enhance the efficacy of current treatment, however clinical trials to test rationally designed combinations of approved drugs are slow and expensive, and limited by our lack of in-depth knowledge of drug specificity. Since many patients already turn to nutraceuticals in hopes of improving their condition, we hypothesized that certain approved drugs could potentially synergize with widely consumed supplements. Following this hypothesis, we devised an alternative screening strategy aimed at taking advantage of a bait compound such as a nutraceutical with potential therapeutic benefits but low potency, by screening chemical libraries for approved drugs that synergize with this companion effector. As a proof of concept, we sought to identify approved drugs with synergetic therapeutic effects toward retinoblastoma cells in combination with the antioxidant resveratrol, popular as a supplement. We systematically tested FDA-approved drugs and known bioactives seeking to identify such pairs, which led to uncovering only a few additive combinations; but to our surprise, we identified a class of anticancer drugs widely used in the clinic whose therapeutic effect is antagonized with resveratrol. Our observations could explain in part why some patients do not respond well to treatment. Our results validate this alternative approach, and we expect that our companion effector strategy could significantly impact both drug discovery and the nutraceutical industry.

Original languageEnglish (US)
Article numbere59156
JournalPloS one
Volume8
Issue number3
DOIs
StatePublished - Mar 19 2013
Externally publishedYes

Fingerprint

Retinoblastoma
Screening
screening
drugs
therapeutics
Dietary Supplements
Pharmaceutical Preparations
functional foods
Therapeutic Uses
resveratrol
Eye Neoplasms
Therapeutics
Small Molecule Libraries
combination drug therapy
Drug Combinations
Drug Discovery
neoplasms
Drug-Related Side Effects and Adverse Reactions
antineoplastic agents
Industry

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Mahida, J. P., Antczak, C., DeCarlo, D., Champ, K. G., Francis, J. H., Marr, B., ... Djaballah, H. (2013). A Synergetic Screening Approach with Companion Effector for Combination Therapy: Application to Retinoblastoma. PloS one, 8(3), [e59156]. https://doi.org/10.1371/journal.pone.0059156

A Synergetic Screening Approach with Companion Effector for Combination Therapy : Application to Retinoblastoma. / Mahida, Jeni P.; Antczak, Christophe; DeCarlo, Daniel; Champ, Kathryn G.; Francis, Jasmine H.; Marr, Brian; Polans, Arthur S.; Albert, Daniel; Abramson, David H.; Djaballah, Hakim.

In: PloS one, Vol. 8, No. 3, e59156, 19.03.2013.

Research output: Contribution to journalArticle

Mahida, JP, Antczak, C, DeCarlo, D, Champ, KG, Francis, JH, Marr, B, Polans, AS, Albert, D, Abramson, DH & Djaballah, H 2013, 'A Synergetic Screening Approach with Companion Effector for Combination Therapy: Application to Retinoblastoma', PloS one, vol. 8, no. 3, e59156. https://doi.org/10.1371/journal.pone.0059156
Mahida, Jeni P. ; Antczak, Christophe ; DeCarlo, Daniel ; Champ, Kathryn G. ; Francis, Jasmine H. ; Marr, Brian ; Polans, Arthur S. ; Albert, Daniel ; Abramson, David H. ; Djaballah, Hakim. / A Synergetic Screening Approach with Companion Effector for Combination Therapy : Application to Retinoblastoma. In: PloS one. 2013 ; Vol. 8, No. 3.
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