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Development of a new small molecule therapeutic for the treatment of resistant breast cancer

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41CA210877-01A1
Agency Tracking Number: R41CA210877
Amount: $329,906.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: 102
Solicitation Number: PA16-303
Timeline
Solicitation Year: 2016
Award Year: 2017
Award Start Date (Proposal Award Date): 2017-09-06
Award End Date (Contract End Date): 2018-09-05
Small Business Information
2645 NINA ST
Pasadena, CA 91107-3710
United States
DUNS: 080112467
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 STAN LOUIE
 (323) 442-3646
 slouie@usc.edu
Business Contact
 NICOS PETASIS
Phone: (213) 740-6673
Email: npetasis@me.com
Research Institution
 UNIVERSITY OF SOUTHERN CALIFORNIA
 
3720 S. FLOWER STREET, 3RD FLOOR
LOS ANGELES, CA 90089-0701
United States

 Nonprofit College or University
Abstract

PROJECT SUMMARYABSTRACTBreast cancer is the second leading cause of death in females with cancerInapproximatelynew cases of invasive breast cancer were diagnosedwhere an estimate ofwas expected to succumb
to their diseaseIt is estimated that one in eight women will develop breast cancer in their lifetimeBreast
cancer is classified into subtypes based on the expression of estrogen receptorERprogesterone receptorPRand amplification of human epidermal growth factor receptorHERThe presence or absence of
these molecular markers has been used to estimate clinical prognosis and to determine treatment response to
current breast cancer therapies targeting these pathwaysDespite these therapeutic advancesbreast cancer
patients that have undetectable ERPR and HERknown as triple negative breast cancerTNBCcannot
benefit from these targeted treatmentsCytotoxic chemotherapy continues to be the primary treatment option
for TNBC patientswhich typically have poor prognosis and significantly lower overall survival when compared
to patients that are ER and or PR positiveThusthere is a major unmet medical need to develop effective
long term therapies for resistant breast cancersincluding TNBCResistant tumors are able to survive and thrive in the hostile tumor microenvironment with low nutrients
and oxygen by adapting to such toxic milieu through various survival mechanismssuch as sustained unfolded
protein responseUPRor persistent endoplasmic reticulum stressERSand autophagyThe hallmark of
ERS is the enhanced expression of chaperone proteins that facilitate the clearance of misfolded proteinsand
as a result they promote anti apoptotic mechanisms and enhance cancer cell survivalThe overexpression of
these chaperone proteins can also confer resistance towards cytotoxic chemotherapyThereforeit is not
surprising that tumor cells with chronic low level of ERS are able to survive and even thrive in inhospitable
environmentsincluding cytotoxic chemotherapyThis project is supported by our findings that even a small
increase in the ER stress levels in tumor cells can surpass a certain threshold where it triggers apoptotic cell
death specifically in tumor cellsBased on our investigations of this novel conceptwe identified a lead compoundwhich was shown to
have efficacy and safety profile suitable to advance for human evaluationThis small molecule was found to
be active in a wide range of cancers includinglungbrainbreastand colon cancersand was shown to be
active alone and in combination with conventional chemotherapy in TNBCsThis project will support the advancement of our lead compound towards clinical developmentThis will be
accomplished by establishing the optimal dosage and frequency when used alone and in combination with
cytotoxic chemotherapyand by determining its pharmacokinetics and pharmacodynamicsThese efforts will
set the stage for completing the preclinical studies of this promising compoundand will help advance it
towards clinical studies for resistant breast cancersincluding TNBC

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

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