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Overcoming antibody-drug conjugate resistance in HER2-positive breast cancer

Year:
2022
Duration:
36 months
Approved budget:
$1,199,994.80
Researchers:
Associate Professor Stephen Jamieson
,
Dr Euphemia Leung
,
Dr Barbara Lipert
,
Dr Tet-Woo Lee
,
Dr Moana Tercel
,
Dr Kimiora Henare
,
Dr Iman Kavianinia
Health issue:
Cancer (oncology)
Proposal type:
Project
Lay summary
Antibody-drug conjugates (ADCs), where potent cytotoxins are linked to antibodies for selective delivery to tumours, are approved for the treatment of HER2-positive breast cancer. However, their use is limited by drug resistance. In this project, we will use CRISPR/Cas9 gene editing techniques to uncover novel genes that are implicated in resistance to different HER2-targeting ADCs. We will gain new understanding of therapeutic resistance to ADCs by knocking out the function of these genes and assessing how that impacts the activity of three different HER2-targeting ADCs. We will target these genes with drugs to identify potential combination therapy strategies to overcome ADC resistance and improve the clinical effectiveness of these agents. Our research will also identify genes that determine sensitivity to ADCs, which may have future clinical utility as patient selection markers to identify the HER2-positive breast cancer patients most like to benefit from ADC therapy.