Oncotarget: Sacituzumab Govitecan in Triple-Negative Breast Cancer

Описание: Oncotarget published this research paper on October 27, 2020, entitled, “Predictive biomarkers for sacituzumab govitecan efficacy in Trop-2-expressing triple-negative breast cancer,” by researchers from Immunomedics, Inc., Morris Plains, NJ.

Abstract:
Sacituzumab govitecan (SG) is an antibody-drug conjugate composed of a humanized anti-Trop-2 IgG antibody conjugated via a hydrolysable linker to SN-38, the topoisomerase I-inhibitory active component of irinotecan. We investigated whether Trop-2-expression and homologous recombination repair (HRR) of SN-38-mediated double-strand DNA (dsDNA) breaks play a role in the sensitivity of triple-negative breast cancer (TNBC) to SG. Activation of HRR pathways, as evidenced by Rad51 expression, was assessed in SG-sensitive cell lines with low and moderate Trop-2-expression (SK-MES-1 squamous cell lung carcinoma and HCC1806 TNBC, respectively), compared to a low Trop-2-expressing, less SG-sensitive TNBC cell line (MDA-MB-231). Further, two Trop-2-transfectants of MDA-MB-231, C13 and C39 (4- and 25-fold higher Trop-2, respectively), were treated in mice with SG to determine whether increasing Trop-2 expression improves SG efficacy. SG mediated less than 2-fold increase in Rad51 in MDA-MB-231 but had no effect in SK-MES-1 or HCC1806, resulting in lower levels of dsDNA breaks in MDA-MB-231. SG and saline produced similar effects in parental MDA-MB-231 tumor-bearing mice (median survival time (MST) = 21d and 19.5d, respectively). However, in mice bearing higher Trop-2-expressing C13 and C39 tumors after Trop-2 transfection, SG provided a significant survival benefit, even compared to irinotecan (MST = 97d vs. 35d for C13, and 81d vs. 28d for C39, respectively; P greater than 0.0007). These results suggest that SG could provide better clinical benefit than irinotecan in patients with HRR-proficient tumors expressing high levels of Trop-2, as well as to patients with HRR-deficient tumors expressing low/moderate levels of Trop-2.

Press release - https://www.oncotarget.com/news/pr/pr...

Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/deta...

DOI - https://doi.org/10.18632/oncotarget.2...

Full text - https://www.oncotarget.com/article/27...

Correspondence to - Thomas M. Cardillo - [email protected]

Keywords - sacituzumab govitecan, Trop-2, biomarker, RAD51, triple-negative breast cancer

About Oncotarget

Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:

SoundCloud -   / oncotarget  
Facebook -   / oncotarget  
Twitter -   / oncotarget  
YouTube -    / oncotargetyoutube  
LinkedIn -   / oncotarget  
Pinterest -   / oncotarget  
Reddit -   / oncotarget  

Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls

Media Contact
[email protected]
18009220957