Schlafen-11 expression is associated with immune signatures and basal-like phenotype in breast cancer

Precision Oncology with Drugs Targeting the Replication Stress, ATR, and Schlafen 11

“…With regards to translating SLFN11 to the clinic, reliable approaches are required to evaluate the SLFN11 status of tumor tissues and circulating tumor cells (CTCs) (Figure 6A). Studies performed at different cancer research centers have established the feasibility of immunohistochemistry (IHC)-based detection of SLFN11 in malignant and adjacent normal tissues [9,11,100,120,138,[140][141][142][143]145]. SLFN11 expression by IHC is also underinvestigation in CTCs from advance prostate cancer and SCLC patients [144,146].…”

Schlafens: Emerging Proteins in Cancer Cell Biology

“…In contrast to the reported positive effects of SLFN5 and SLFN12 in breast cancer, high SLFN11 expression correlates with more aggressive breast cancer tumors with signs of immune activation (basal-like phenotype, higher histological grade, younger age), while lower SLFN11 expression is noted in the luminal, less aggressive neoplasms characterized by low immune activation [ 17 ]. Moreover, SLFN11 positively correlates with markers of lymphocytic tumor infiltration such as CD3 and CD8 in breast cancer [ 17 ]. Interestingly, similar to SLFN5 and SLFN12, SLFN11 overexpression is independently associated with a better prognosis.…”

“…Interestingly, similar to SLFN5 and SLFN12, SLFN11 overexpression is independently associated with a better prognosis. However, patients with high SLFN11 and undergoing hormone therapy have a short-term worse prognosis in the first two years [ 17 ]. This could be because high SLFN11 breast cancers are mostly ER-negative, basal-like phenotype that are known for their poor response to hormonal therapy [ 17 , 93 ].…”

“…However, patients with high SLFN11 and undergoing hormone therapy have a short-term worse prognosis in the first two years [ 17 ]. This could be because high SLFN11 breast cancers are mostly ER-negative, basal-like phenotype that are known for their poor response to hormonal therapy [ 17 , 93 ]. Another study examined the patient-derived xenografts (PDXs) response to DDA and has shown SLFN11 is significantly elevated in metastatic tumors compared to non-metastatic ones, and high SLFN11 metastatic PDXs showed better response to therapy with DNA damaging agents [ 94 ].…”

“…Schlafens were initially demonstrated to be differentially expressed in lymphoid tissue and thus believed to play a role in the maturation and activation of thymocytes [ 1 ]. However, further exploration has extended our understanding of Schlafen function to include roles in cell proliferation [ 8 , 9 ], cell differentiation [ 10 , 11 ], viral replication [ 12 , 13 ], cancer biology [ 14 , 15 , 16 , 17 ], and sensitizing cancer cells to chemotherapy [ 18 , 19 , 20 , 21 , 22 , 23 ].…”