Project description:Thirteen HER2 positive breast cancer cell lines were screened with 22 commercially available compounds, mainly targeting proteins in the ErbB2 signaling pathway, and the molecular mechanisms related to treatment response were sought. To search for response predictors, genomic and transcriptomic profiling, PIK3CA mutations and PTEN status were associated to the drug responses and several genes involved in the response of the compounds were identified.

2015-01-30 | GSE58700 | GEO

Drug screening and genomic analyses of HER2 positive breast cancer cell lines reveal predictors for treatment response [CGH]

2015-01-30 | GSE58886 | GEO

Drug screening and genomic analyses of HER2 positive breast cancer cell lines reveal predictors for treatment response [Expression profiling]

2015-01-30 | E-GEOD-58700 | biostudies-arrayexpress

Drug screening and genomic analyses of HER2 positive breast cancer cell lines reveal predictors for treatment response [CGH]

2015-01-30 | E-GEOD-58886 | biostudies-arrayexpress

MicroRNA Predictors of Miscarriage

Project description:MicroRNA Predictors of Miscarriage

| PRJNA877004 | ENA

A preclinical platform for assessing anti-tumor effects and systemic toxicities of cancer drug targets

Project description:Anti-cancer drug development campaigns often fail due to an incomplete understanding of the therapeutic index differentiating the efficacy of the agent against the cancer and its on-target toxicities to the host. To address this issue, we established a versatile preclinical platform in which genetically defined cancers are produced using somatic tissue engineering in transgenic mice harboring a Doxycycline-inducible short hairpin RNA against the target of interest. In this system, target inhibition is achieved by addition of doxycycline, enabling simultaneous assessment of efficacy and toxicity in the same animal. As proof-of-concept, we focused on CDK9 — a cancer target whose clinical development has been hampered by compounds with poorly understood target specificity and unacceptable toxicities. We systematically compared phenotypes produced by genetic Cdk9 inhibition to those achieved using a recently developed highly specific small molecule CDK9 inhibitor and found that both perturbations led to robust anti-tumor responses. Remarkably, non-toxic levels of CDK9 inhibition could achieve significant treatment efficacy, and dose-dependent toxicities produced by prolonged CDK9 suppression were largely reversible upon Cdk9 restoration or drug withdrawal. Overall, these results validate a versatile in vivo target validation platform that can be employed for rapid triaging of therapeutic targets and lend support to efforts aimed at advancing CDK9 inhibitors for cancer therapy.

2022-03-30 | GSE196783 | GEO

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