Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metastasis to multiple organs is the primary cause of mortality in breast cancer patients. The poor prognosis for patients with metastatic breast cancer and toxic side effects of currently available treatments necessitate the development of effective tumor-selective therapies. Neural stem cells (NSCs) possess inherent tumor tropic properties that enable them to overcome many obstacles of drug delivery that limit effective chemotherapy strategies for breast cancer. We report that increased NSC tropism to breast tumor cell lines is strongly correlated with the invasiveness of cancer cells. Interleukin 6 (IL-6) was identified as a major cytokine mediating NSC tropism to invasive breast cancer cells. We show for the first time in a preclinical mouse model of metastatic human breast cancer that NSCs preferentially target tumor metastases in multiple organs, including liver, lung, lymph nodes, and femur, versus the primary intramammary fat pad tumor. For proof-of-concept of stem cell-mediated breast cancer therapy, NSCs were genetically modified to secrete rabbit carboxylesterase (rCE), an enzyme that activates the CPT-11 prodrug to SN-38, a potent topoisomerase I inhibitor, to effect tumor-localized chemotherapy. In vitro data demonstrate that exposure of breast cancer cells to conditioned media from rCE-secreting NSCs (NSC.rCE) increased their sensitivity to CPT-11 by 200-fold. In vivo, treatment of tumor-bearing mice with NSC.rCE cells in combination with CPT-11 resulted in reduction of metastatic tumor burden in lung and lymph nodes. These data suggest that NSC-mediated enzyme/prodrug therapy may be more effective and less toxic than currently available chemotherapy strategies for breast cancer metastases.
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PMID:Human neural stem cell tropism to metastatic breast cancer. 2208 33

Patients with HR+/HER2- metastatic breast cancer (MBC) whose cancers have progressed despite conventional therapies represent an unmet clinical need. Trop-2, a transmembrane calcium signal transducer, is highly expressed in MBC and plays a role in tumor growth and progression. Sacituzumab govitecan (SG) is a novel antibody-drug conjugate comprising an Trop-2 antibody coupled to SN-38, the active metabolite of irinotecan, via a unique hydrolyzable linker. SG has demonstrated promising activity in a Phase I/II IMMU-132-01 basket study in heavily pretreated solid tumors, including HR+/HER2- MBC. We describe the registrational Phase III TROPiCS-02 study (NCT03901339), evaluating SG versus treatment of physician's choice in HR+/HER2- MBC. Trial registration number: NCT03901339.
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PMID:TROPiCS-02: A Phase III study investigating sacituzumab govitecan in the treatment of HR+/HER2- metastatic breast cancer. 3222 49