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Develop a new cisplatin based drug combination with reduced ototoxicity

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41DC016575-01
Agency Tracking Number: R41DC016575
Amount: $224,700.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NIDCD
Solicitation Number: PA16-303
Solicitation Year: 2016
Award Year: 2017
Award Start Date (Proposal Award Date): 2017-07-05
Award End Date (Contract End Date): 2018-01-31
Small Business Information
Saint Louis, MO 63130-4309
United States
DUNS: 968854815
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (314) 620-5737
Business Contact
Phone: (314) 620-5737
Research Institution
1960 Kenny Road
Columbus, OH 43210-1016
United States

 Nonprofit college or university

In spite of recent new drug developments platinum based drugs such as cisplatin are still
widely used to treat solid organ malignancies Besides its limited efficacy serious side effects have
been associated with the use of cisplatin such as bilateral and irreversible hearing loss In the
cochlea cisplatin can trigger the production of reactive oxygen species and activate several other
signaling pathways A variety of agents mainly based on their antioxidant properties have been
tested against cisplatin induced ototoxicity However many of them show limited efficacies and also
interfere with the therapeutic effect of cisplatin Extensive in vitro studies have indicated that
flunarizine Sibelium a drug that blocks T type calcium channels can protect cochlear cells against
cisplatin induced cytotoxicity This drug also has strong anti tumor activities that act synergistically on
several important aspects of cancer treatment Our preliminary studies have found that flunarizine
can synergistically induce cell death with cisplatin in one lung cancer cell line and it can also protect
noise induced hearing loss Based on these findings we propose to develop a new cancer drug
combination by testing whether flunarizine can synergistically induce cancer cell death with cisplatin
and at the same time prevent cisplatin induced ototoxicity Because lung cancer is the leading cause
of cancer related death globally and cisplatin is widely used to treat this disease here we will first
determine the cytotoxic effects of flunarizine and cisplatin in two lung cancer cell lines A and
H and determine whether flunarizine and cisplatin have synergistic effects in these cancer cells
when used in combination Aim We will then determine whether flunarizine can prevent cisplatin
induced ototoxicity in vivo Aim
In short based on previous studies and our preliminary data our project goal is to repurpose
flunarizine to combine with cisplatin against solid tumors with a focus on lung cancer This project will
generate data important to complete an Investigational New Drug IND enabling data package for
future clinical studies The ultimate goal is to develop an effective cancer drug combination with fewer
side effects Public Health Relevance Narrative
Platinum based drugs such as cisplatin are still widely used to treat solid tumors with
limited efficacies and serious side effects Our method has the potential to reduce the
serious side effect of ototoxicity and increase the efficacy of cisplatin by introducing a
novel drug combination

* Information listed above is at the time of submission. *

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