Fig 1: SLFN11 does not predict olaparib sensitivity independent of BRCA status.a–d Cox proportional hazards model by SLFN11 high (>30 H-score SLFN11) vs. low SLFN11 ( = 30 H-score SLFN11) subgroups in platinum-sensitive serous ovarian carcinoma patients treated with either placebo or olaparib for (a) progression-free survival (PFS) in BRCA wild-type patients, b PFS in BRCA mutant patients, c Overall survival (OS) in BRCA wild-type patients, d OS in BRCA mutant patients. Events table with patients at risk shown for each timepoint. VUS BRCAm patients included in the BRCAwt group.
Fig 2: The SLFN11 and ATR pathways in response to RepStress. SLFN11 irreversibly blocks DNA replication under RepStress by promoting chromatin opening, blocking the CMG helicase complex, and promoting the degradation of CDT1 (see Section 5.1 for details). In contrast, ATR transiently halts DNA replication by arresting cell cycle and prohibiting origin firing, thereby enabling homology-directed repair (HDR).
Fig 3: SLFN11 not significantly associated with sensitivity to the paclitaxel–carboplatin doublet in serous ovarian cancers.a Prevalence of SLFN11 by IHC H-score in serous ovarian cancer patient biopsies (n = 151), cut-off depicting the high and low SLFN11 subgroups shown, b representative images of high and low SLFN11 tumours. Black arrow indicates SLFN11-positive stromal cells used as an internal control. Scale bars at 100 µm. c SLFN11 H-score of patients divided by extreme good and poor clinical responders to carboplatin and paclitaxel doublet therapy. Median ± interquartile range shown. d SLFN11 IHC protein expression by H-score compared to NanoString quantified SLFN11 gene expression in the HGSOC patients. Dotted line indicates gene expression threshold that distinguishes positive from negative SLFN11 patients. Patients with sub-clonal SLFN11 indicated by a red dot. e, f Kaplan–Meier survival curves of (e) progression-free interval (PFI) and (f) overall survival (OS) of high (>30 H-score SLFN11) vs. low SLFN11 ( = 30 H-score SLFN11) subgroups in the 34 patients with high-grade serous ovarian cancer treated with carboplatin and paclitaxel doublet. Events table with patients at risk shown for each timepoint.
Fig 4: Elevated SLFN11 levels in HGSOC patients confers sensitivity to olaparib.a Cox proportional hazards model of progression-free survival (PFS) of high (>30 H-score SLFN11) vs. low SLFN11 ( = 30 H-score SLFN11) subgroups in platinum-sensitive serous ovarian carcinoma patients treated with either placebo or olaparib. b Overall survival (OS) of high vs. low SLFN11 in the same study. Events table with patients at risk shown for each timepoint.
Fig 5: SLFN11 protein levels are variable across tumour types and higher levels are found in more aggressive cancer subtypes.a SLFN11 expression in normal tissues, arrows indicate (from left to right); negative breast lobular cells, positive (red) and negative (blue) prostatic cells, positive lymphocytes, positive bronchial epithelial cells, negative colon epithelial cells. Negative Langerhans islets (blue circle) and positive cluster of acinar cells (red circle) also shown. b SLFN11 prevalence in various cancer types from multi-tumour tissue microarrays (TMAs), expression of SLFN11 shown as percent of positive tumour cells when internal control staining was acceptable. Median given (green) for each cancer type. c Example images of SLFN11 IHC staining in head and neck, thyroid, lymphoma and prostate cancers (Ca). d, e Breakdown of the SLFN11 protein levels by: d breast cancer subtype; oestrogen receptor-positive (ER + ), human epidermal growth factor receptor 2 (HER2 + ), triple-negative breast cancer (TNBC), invasive lobular breast cancer (ILC) and e thyroid cancer subtype; papillary and follicular. f–h SLFN11 expression in colorectal cancer (CRC) patients (n = 144) subcategorised by clinical patient information: f presence of metastasis or not; g tumour grade, h disease stage. Data shown as median ± interquartile range. *P value <0.05 by Mann–Whitney test. Black arrows are stromal and endothelial cells. Scale bars at 100 µm.
Supplier Page from Abcam for Anti-SLFN11 antibody