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Association details:
| Biomarker: | EGFR mutation |
|---|---|
| Cancer: | Non Small Cell Lung Cancer |
| Drug: | Tagrisso (osimertinib) (EGFR inhibitor) + patritumab deruxtecan (U3-1402) (Topoisomerase I inhibitor, HER3-targeted antibody-drug conjugate) |
| Direction: | Sensitive |
Evidence:
Source:
Title:
HER3 Augmentation via Blockade of EGFR/AKT Signaling Enhances Anticancer Activity of HER3-Targeting Patritumab Deruxtecan in EGFR-Mutated Non–Small Cell Lung Cancer
Published date:
12/17/2021
Excerpt:
The anticancer efficacy of HER3-DXd and osimertinib was evaluated in EGFR-mutated NSCLC cells…. An in vitro study also showed that EGFR-TKI increased HER3 expression, repressed AKT phosphorylation in multiple EGFR-mutated cancers, and enhanced the anticancer activity of HER3-DXd....Our findings help clarify the mechanisms of HER3 regulation in EGFR-mutated NSCLC tumors and highlight a rationale for combination therapy with HER3-DXd and EGFR-TKI in EGFR-mutated NSCLC.
DOI:
10.1158/1078-0432.CCR-21-3359
Source:
Title:
Abstract 5192: EGFR inhibition enhances the cellular uptake and antitumor activity of the novel HER3 antibody drug conjugate U3-1402
Published date:
05/15/2020
Excerpt:
In long-term in vitro cell growth assays, the combination of osimertinib and U3-1402 was superior to single agent U3-1402 in four EGFR-mutant cell lines.
DOI:
10.1158/1538-7445.AM2020-5192
Source:
Title:
An HER3-targeting antibody-drug conjugate incorporating a DNA topoisomerase I inhibitor U3-1402 conquers EGFR tyrosine kinase inhibitor-resistant NSCLC
Excerpt:
In addition, administration of U3-1402 notably repressed growth of EGFR-TKI osimertinib-resistant PC9AZDR7 xenograft tumours, and that PC9AZDR7 cells expressed five times greater cell surface HER3 than PC9 cells...Our results indicate that administration of U3-1402 alone or in combination with an EGFR-TKI may have potential as a novel therapy for EGFR-TKI-resistant EGFR-mutant NSCLC.
DOI:
10.1038/s41388-018-0517-4
