We present a case report of a patient with metastatic small cell neuroendocrine carcinoma of the breast (SCNCB), a high-grade neuroendocrine triple-negative breast cancer, who achieved a complete response after two cycles of sacituzumab govitecan-hziy (SG) (Trodelvy) as third-line systemic therapy. She originally presented with estrogen receptor-positive disease, and we were able to clearly demonstrate transformation into triple-negative SCNCB via serial tissue biopsies. This is the first reported case of SG for SCNCB, and it shows an outstanding response in a patient who had undergone prior systemic therapies. Clinical trials are needed to address the potential role of TROP2 inhibition and the use of SG as a therapy for SCNCB.
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http://dx.doi.org/10.1177/17588359251322003 | DOI Listing |
Ther Adv Med Oncol
February 2025
David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
We present a case report of a patient with metastatic small cell neuroendocrine carcinoma of the breast (SCNCB), a high-grade neuroendocrine triple-negative breast cancer, who achieved a complete response after two cycles of sacituzumab govitecan-hziy (SG) (Trodelvy) as third-line systemic therapy. She originally presented with estrogen receptor-positive disease, and we were able to clearly demonstrate transformation into triple-negative SCNCB via serial tissue biopsies. This is the first reported case of SG for SCNCB, and it shows an outstanding response in a patient who had undergone prior systemic therapies.
View Article and Find Full Text PDFClin Cancer Res
February 2025
Gilead Sciences, Inc., United States.
Sacituzumab govitecan (SG), a Trop-2-directed antibody-drug conjugate, is currently approved to treat metastatic triple-negative breast cancer and HR+/HER2- breast cancer, and is under clinical investigation for a range of other tumor types. This review describes its mode of action, development, and clinical outcomes. SG is composed of SN-38 (a topoisomerase I inhibitor derived from irinotecan) covalently linked to an anti-Trop-2 monoclonal antibody (sacituzumab; hRS7) via a hydrolysable CL2A linker.
View Article and Find Full Text PDFEur J Med Chem
March 2025
Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, 201210, China. Electronic address:
Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy with poor prognosis. Antibody-drug conjugates (ADCs) and their combinations with various anti-tumor drugs have made great progress. Camptothecin, and its derivatives (Dxd, SN-38 or exatecan) targeted TOP1 are effective payloads due to their potent anti-tumor activity.
View Article and Find Full Text PDFFront Immunol
December 2024
Myeloid Therapeutics, Inc., Cambridge, MA, United States.
Introduction: The approval of chimeric antigen receptor (CAR) T cell therapies for the treatment of B cell malignancies has fueled the development of numerous cell therapies. However, these cell therapies are complex and costly, and unlike in hematological malignancies, outcomes with most T cell therapies in solid tumors have been disappointing. Here, we present a novel approach to directly program myeloid cells by administering novel TROP2 CAR mRNA encapsulated in lipid nanoparticles (LNPs).
View Article and Find Full Text PDFBioorg Med Chem Lett
April 2025
Pinotbio, Inc Suwon, Gyeonggi-do 16506, South Korea.
FL118, a camptothecin derivative with dual mechanisms of action through topoisomerase I inhibition and proteasome-mediated degradation of anti-apoptotic proteins exhibits potent anti-tumor activity while remaining resistant to drug efflux transporters. This work describes the targeted delivery of FL118 to tumors via antibody-drug conjugates (ADCs) using the pH-sensitive CL2A linker. ADCs targeting Trop2, HER2, and EGFR exhibited potent in vitro cytotoxicity, with IC values as low as 0.
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