Grant: Project Grant
University of Alberta
$841,500.00
Development of Small Macrocyclic Antibody-Like Scaffolds (SMALS) for therapeutic inhibition of Nodal
FY 2019-20
Summary
NODAL is a protein that is normally in stem cells but that re-emerges in cancer, where it promotes cancer progression and metastasis. We have recently shown that NODAL may drive chemoresistance in ovarian cancer. Accordingly, inhibiting NODAL seems to improve the efficacy of carboplatin in mice bearing AVATAR-like ovarian cancer patient derived xenografts. Because NODAL is not in normal adult tissues, it can be targeted without causing major side effects. In this project, we will strive to develop drugs against NODAL, with the intention of finding a better way to treat ovarian cancer patients. These new anti-NODAL drugs will consist of Small Macrocyclic Antibody-Like Scaffolds (SMALS) which are made by chemical synthesis and are designed to block NODAL and to stay in the circulation so that they may be one day given to patients. We will test these drugs to see how well they work to kill ovarian cancer cells in the lab and in mouse models of cancer. If successful, we will have developed a new drug to be tested in ovarian cancer patients.
Department
Program
Project Grant
Recipient
Location
Alberta, Canada
Recipient Type
Academia
Type
Grant
Source
CIHR Funding Decisions Database
As published
Id
408349
Name
Derda Ratmir
Region
Alberta
Country
Canada
Orgtype
Institution Paid; Research Institution
Instname2
Cancer Research
Theme2
Biomedical
Prcname2
Pharmaceutical Sciences
Projecttitle
Development of Small Macrocyclic Antibody-Like Scaffolds (SMALS) for therapeutic inhibition of Nodal
Programtype2
Operating Grants
Orgnameinp2
University of Alberta
Cihramount2
$841,500
Cihrequipment2
$0
Programname2
Project Grant
Keyworddelim
Bicyclic Peptides; Cancer Stem Cells; Drug Discovery; Genetically-Encoded Libraries; Hit To Lead Optimization; Macrocyclic Peptides; Nodal; Therapeutic Inhibitors
Abstract
NODAL is a protein that is normally in stem cells but that re-emerges in cancer, where it promotes cancer progression and metastasis. We have recently shown that NODAL may drive chemoresistance in ovarian cancer. Accordingly, inhibiting NODAL seems to improve the efficacy of carboplatin in mice bearing AVATAR-like ovarian cancer patient derived xenografts. Because NODAL is not in normal adult tissues, it can be targeted without causing major side effects. In this project, we will strive to develop drugs against NODAL, with the intention of finding a better way to treat ovarian cancer patients. These new anti-NODAL drugs will consist of Small Macrocyclic Antibody-Like Scaffolds (SMALS) which are made by chemical synthesis and are designed to block NODAL and to stay in the circulation so that they may be one day given to patients. We will test these drugs to see how well they work to kill ovarian cancer cells in the lab and in mouse models of cancer. If successful, we will have developed a new drug to be tested in ovarian cancer patients.
Competitiondate
201909
Approvedterm2
5 yrs 0 mth
Pinamesdelim
Derda, Ratmir
Approvedterm
5 ans 0 mois
Cihrcontribution2
~ $841,500~ $0~
