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• W4307460432 abstract "Background: Sortilin (SORT1), or neurotensin receptor-3, is a scavenging receptor in the Vacuolar Protein Sorting 10 protein (Vps10p) family. SORT1 is involved in the internalization and trafficking of its ligands through an endocytic process and is reported to play a role in cancer cell survival and progression, making SORT1 a candidate for novel drug delivery. The pattern and prevalence of SORT1 expression in different healthy and cancer tissues is still not well understood. Material and methods: To gain better understanding about the expression of SORT1, screening of healthy and cancer tissue microarrays (TMAs) was undertaken using an immunohistochemistry (IHC) method. A total of 19 TMAs were screened, 4 for breast cancer (including triple-negative breast cancer (TNBC)), 3 for ovarian cancer, 2 for endometrial cancer, 3 for melanoma, 3 for colorectal cancer, 3 for pancreatic cancer and 1 for different healthy tissues. A total of 1222 cancer cores were evaluable and scored using a H-score ranging from 0 to 300, where 0 corresponds to no cell stained for SORT1, while 300 corresponds to strong SORT1 staining in all cells. Results: A H-score ≥100 was observed in 88% of breast cancers (n = 195), 70% of TNBC (n = 171), 75% of ovarian cancers (n = 249), 91% of endometrial cancers (n = 76), 88% of melanomas (n = 158), 55% of colon cancers (n = 195), and 26% of pancreatic cancers (n = 178). The corresponding average H-scores were 160, 135, 142, 175, 163, 99 and 54, respectively. Sub-analyses of SORT1 expression by tumor histological subtype and grade are on-going, and additional TMAs are being screened. A total of 160 healthy tissue cores were also evaluated. Interestingly, SORT1 staining was either negative (null) or low for most healthy tissues including lung, stomach, liver, ovary, prostate, lymph node, esophagus, small intestine, cervix, skin, spleen, bone marrow and thymus. Some healthy tissues had moderate or strong staining in >10% of cells, i.e. colonic mucosa, rectal epithelium, pancreatic islets and vessels, breast lobules, testicular spermatids and Sertoli cells, kidney tubules and cerebral neuronal cells and astrocytes. Conclusions: SORT1 is currently been studied as a cancer target in a first-in-human (FIH) study of a peptide-drug conjugate (clinicaltrial.gov: NCT04706962). Overall, these results suggest that SORT1 is highly expressed in multiple tumors and is a promising target for the delivery and internalization of cancer therapeutic agents. Conflict of interest: Other Substantive Relationships: Christian Marsolais is Senior VP and Chief Medical Officer of Theratechnologies Inc., for which he sits on the executive leadership team (salary and bonus) and has shares of the company." @default.
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• W4307460432 date "2022-10-01" @default.
• W4307460432 modified "2023-10-18" @default.
• W4307460432 title "Expression of the sortilin 1 receptor (SORT1) in healthy and tumor tissues" @default.
• W4307460432 doi "https://doi.org/10.1016/s0959-8049(22)01112-1" @default.
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