Sacituzumab Govitecan with Platinum Chemotherapy: Antitumor Effects | Oncotarget

1 views

|

February 28, 2024

  • Share
  • Oncotarget published this research paper on February 22, 2024 in Volume 15, entitled, “Sacituzumab govitecan plus platinum-based chemotherapy mediates significant antitumor effects in triple-negative breast, urinary bladder, and small-cell lung carcinomas" by researchers from Immunomedics, Inc., Morris Plains, NJ 07950 now acquired by Gilead Sciences, Inc., Foster City, CA; Gilead Sciences, Inc., Foster City, CA. DOI - https://doi.org/10.18632/oncotarget.28559 Correspondence to - Thomas M. Cardillo - Thomas.Cardillo1@Gilead.com Abstract Sacituzumab govitecan (SG) is an antibody-drug conjugate composed of an anti-Trop-2-directed antibody conjugated with the topoisomerase I inhibitory drug, SN-38, via a proprietary hydrolysable linker. SG has received United States Food and Drug Administration (FDA) approval to treat metastatic triple-negative breast cancer (TNBC), unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer, and accelerated approval for metastatic urothelial cancer. We investigated the utility of combining SG with platinum-based chemotherapeutics in TNBC, urinary bladder carcinoma (UBC), and small-cell lung carcinoma (SCLC). SG plus carboplatin or cisplatin produced additive growth-inhibitory effects in vitro that trended towards synergy. Immunoblot analysis of cell lysates suggests perturbation of the cell-cycle and a shift towards pro-apoptotic signaling evidenced by an increased Bax to Bcl-2 ratio and down-regulation of two anti-apoptotic proteins, Mcl-1 and survivin. Significant antitumor effects were observed with SG plus carboplatin in mice bearing TNBC or SCLC tumors compared to all controls (P < 0.0062 and P < 0.0017, respectively) and with SG plus cisplatin in UBC and SCLC tumor-bearing animals (P < 0.0362 and P < 0.0001, respectively). These combinations were well tolerated by the animals. Combining SG with platinum-based chemotherapeutics demonstrates the benefit in these indications and warrants further clinical investigation. Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28559 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, sacituzumab govitecan, Trop-2, SN-38, carboplatin, cisplatin About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

    Cancer ResearchCell ScienceDrug Discovery

    Keep up to date with all your favourite videos and channels.

    Get personalised notifications on new releases and channel content by subscribing to the LabTube eNewsletter.