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Additional file 1. Supplementary material. Supplementary Table 1. Summary of previous studies on Aβ, tau, and p-tau (detected in the plasma nEV) as biomarkers of AD. Supplementary Table 2. Quality control of the nEV protein. Supplementary Table 3. Baseline characteristics of all subjects with plasma Aβ levels by clinical diagnosis. Supplementary Table 4. Comparisons between participants with and without sMRI or scales data. Supplementary Table 5. Relationships between nEV Aβ42 and age, sex, group, and APOE ε4 status. Supplementary Table 6. Relationship between nEV Aβ42 and AV45 SUVR. Supplementary Table 7. Relationship between baseline nEV Aβ42 and cognitive scales. Supplementary Table 8. Relationship between baseline nEV Aβ42 and brain regional volume. Supplementary Figure 1. Typical TEM images of nEV. Supplementary Figure 2. Typical NTA results. Supplementary Figure 3. NTA results of enrolled subjects. Supplementary Figure 4. Western blot characterization of nEVs. Supplementary Figure 5. nEV Aβ concentrations in different diagnostic groups and the ROC curves. Supplementary Figure 6. Plasma Aβ concentrations in different diagnostic groups.Supplementary Figure 7. Association between nEV Aβ42 concentrations and MoCA-B scale. Supplementary Figure 8. Association between nEV Aβ42 concentrations and baseline brain regional volume. Supplementary Figure 9. Association between nEV Aβ42 concentrations and longitudinal changes in brain regional volume.

Additional file 1: Supplementary Table 1. The ROI-based brain regions with significant differences between SCD and NC by 10 times repeated cross-validations. Supplementary Table 2. AUCs of the ROC curves. Supplementary Figure 1. Flowchart shows selection of subjects. Supplementary Figure 2. The single-subject RMTG SUVR maps of NC, SCD, aMCI, ADD, and DLB individuals from [18F] FDG-PET scans. Supplementary Figure 3. ROC curves.

Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) are an exciting class of anticancer drugs, which have revolutionized the management of BRCA mutant/homologous recombination-deficient recurrent high-grade serous ovarian cancer (HGSOC). With three PARPi now approved by the US Food and Drug Administration, olaparib (Lynparza™), niraparib (Zejula™), and rucaparib (Rubraca™) in 2014 (and 2017 for the tablet formulation), 2016, and 2017, respectively, these drugs have now entered routine clinical practice. The marked single-agent efficacy of PARPi either as maintenance following response to platinum-based chemotherapy or as up-front treatment in these indications is based on the well-known concept of synthetic lethality. PARPi themselves work by blocking the repair of single-strand DNA breaks by the base excision/single-strand break repair pathway and can also be directly cytotoxic by the mechanism of PARP trapping. The greatest benefit in terms of progression-free survival, in all three PARPi maintenance registration studies, was seen in women with platinum-sensitive BRCA mutation-associated HGSOC. However, it is clear that non-BRCA HGSOC can benefit from PARPi and the ongoing challenge of biomarker driven studies is how best to define these patients. PARPi are well tolerated, but more information is needed to assess the longer-term/later onset toxicities as these agents are investigated in the first-line setting. The future direction and challenges for PARPi will be to continue to expand beyond BRCA and ovarian cancer by identifying molecular or functional signatures of response; to see if the durable responses in ovarian cancer can be improved and efficacy can be achieved in other cancer sub-types by combining with novel targeted agents. This review summarizes the development of PARPi as a class in ovarian cancer with particular focus on the PARPi rucaparib.