Award

Biomarkers for predicting response to Hsp90 therapy

Description: PUBLIC HEALTH RELEVANCE: Despite of the large number of potential new agents entering clinical evaluation every year, only 5% to 8% ever reach registration. Of particular concern is the high rate of failures in Phase 3, where an estimated 50% of oncology agents are stopped in development. Such failures are especially expensive and deprive many patients of potentially more effective treatments. These dire statistics clearly speak for the need to discover and implement predictive biomarkers for patient selection and trial enrichment. What have we learned from the results obtained in the last years with targeted agents? When a new drug has been administered, either as a single agent or in addition to chemotherapy in a study population not selected by any biomarker, most trials have produced negative results, while in a small minority of cases a statistically significant benefit has been demonstrated. This benefit, however, consisted -- at best -- of a small or moderate absolute prolongation of overall survival. On the other hand, examples of a greater absolute benefit obtained with the use of targeted agents based on a biomarker-driven patient selection are constantly increasing. Biomarkers provide the possibility to use tumor and patient characteristics to integrate an accurate predictor of efficacy with a specific mechanism based therapy, guiding the selection of treatment for each individual patient. In particular, a validated predictive marker can prospectively identify individuals who are likely to have a positive clinical outcome from a specific treatment. The technology described in this grant application provides an approach to improve our use of Hsp90 cancer therapeutics and promises to revolutionize the way we implement them in oncology. In short, we offer a way to identify which patients will benefit from these therapies. Itis the quest of modern oncology to find such technologies and this proposal is first ever to attempt to do so non-invasively in both blood cancers and solid tumors.
Funding type: research
Funder scheme: R01
Start date: 2013-07-01
End date: 2019-04-30
Investigator: GABRIELA CHIOSIS
Institution: SLOAN-KETTERING INST CAN RESEARCH
Funded outputs count: 153
Funder award ID: R01CA172546
OpenAlex ID: G439846533
2025 · Anna Rodina, Hediye Erdjument-Bromage, et al. · Journal of Visualized Experiments
2025 · Feixia Chu, Sahil Sharma, et al. · Trends in Biochemical Sciences · 16
2025 · Chiranjeevi Pasala, Chander S. Digwal, et al. · RSC Chemical Biology · 9
2024 · Tanaya Roychowdhury, Seth W. McNutt, et al. · Nature Communications · 29
2024 · Sonia Mahajan, Milan Grkovski, et al. · Clinical and Translational Imaging · 2
2024 · Chiranjeevi Pasala, Tanaya Roychowdhury, et al. · Biomolecules · 57
2023 · Gabriela Chiosis, Chander S. Digwal, et al. · Nature Reviews Molecular Cell Biology · 203
2023 · Tanaya Roychowdhury, Anand R. Santhaseela, et al. · Methods in molecular biology · 7
2022 · Stephen D. Ginsberg, Sahil Sharma, et al. · Trends in Pharmacological Sciences · 31
2021 · Alexander Bolaender, Danuta Zatorska, et al. · Nature Communications · 34
2020 · Mark P. S. Dunphy, Nagavarakishore Pillarsetty · Cancers · 10
2020 · Kimihito C. Kawabata, Hongliang Zong, et al. · Blood · 42
2020 · Jiang Yang, Tai Wang, et al. · Nature Biomedical Engineering · 94
2020 · Mark P.S. Dunphy, Christina Pressl, et al. · Clinical Cancer Research · 30
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