| RRC ID |
44353
|
| 著者 |
Mahida JP, Antczak C, Decarlo D, Champ KG, Francis JH, Marr B, Polans AS, Albert DM, Abramson DH, Djaballah H.
|
| タイトル |
A synergetic screening approach with companion effector for combination therapy: application to retinoblastoma.
|
| ジャーナル |
PLoS One
|
| 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.
|
| 巻・号 |
8(3)
|
| ページ |
e59156
|
| 公開日 |
2013-1-1
|
| DOI |
10.1371/journal.pone.0059156
|
| PII |
PONE-D-12-40695
|
| PMID |
23527118
|
| PMC |
PMC3602587
|
| MeSH |
Antineoplastic Agents / pharmacology*
Antineoplastic Agents / therapeutic use
Cell Line, Tumor
Cell Survival / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor* / methods
Drug Synergism
High-Throughput Screening Assays* / methods
Humans
Inhibitory Concentration 50
Reproducibility of Results
Resveratrol
Retinal Neoplasms / drug therapy
Retinoblastoma / drug therapy
Small Molecule Libraries
Stilbenes / pharmacology
Stilbenes / therapeutic use
|
| IF |
2.74
|
| 引用数 |
15
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
NCC-RbC-60(RCB2213)
NCC-RbC-51(RCB2206) |
