Sandra E. Spencer Miko
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View article: Cystathionine gamma‐lyase‐mediated hypoxia inducible factor 1‐alpha expression drives clear cell ovarian cancer progression
Cystathionine gamma‐lyase‐mediated hypoxia inducible factor 1‐alpha expression drives clear cell ovarian cancer progression Open
Clear cell ovarian cancer (CCOC) is the second most common ovarian cancer subtype, accounting for 5%–11% of ovarian cancers in North America. Late‐stage CCOC is associated with a worse prognosis compared to other ovarian cancer histotypes,…
View article: Prognostically favorable immune responses to ovarian cancer are distinguished by self-reactive intra-epithelial plasma cells
Prognostically favorable immune responses to ovarian cancer are distinguished by self-reactive intra-epithelial plasma cells Open
SUMMARY Tumor-infiltrating B cells (TIL-Bs) are strongly associated with patient survival; however, the underlying mechanisms are poorly understood. Using integrated single-cell and spatial biology approaches, we defined at clonal resoluti…
View article: Data Independent Acquisition to Inform the Development of Targeted Proteomics Assays Using a Triple Quadrupole Mass Spectrometer
Data Independent Acquisition to Inform the Development of Targeted Proteomics Assays Using a Triple Quadrupole Mass Spectrometer Open
Mass spectrometry based targeted proteomics methods provide a sensitive and high-throughput analysis of selected proteins. To develop a targeted bottom-up proteomics assay, peptides must be evaluated as proxies for the measurement of a pro…
View article: Supplementary Table S1 from Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer
Supplementary Table S1 from Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer Open
Supplementary Table S1: Patient characteristics. Age, ECOG performance status, HER2 status, steroid hormone receptor status, and biopsy site data are summarized.
View article: Supplementary Fig. S3 from Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer
Supplementary Fig. S3 from Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer Open
Supplementary Fig. S3: Proteomic profiling. Heatmap showing proteins with a moderate consensus across the patient cohort (|FC| > 20% and uncorrected p-value < 0.05). Peptide coverage for each TMT plex is shown on the left.
View article: Supplementary Fig. S1 from Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer
Supplementary Fig. S1 from Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer Open
Supplementary Fig. S1: Pharmacokinetic data. Circulating tomivosertib concentrations in healthy volunteers showing similarity of administering 100 mg tomivosertib with food or 200 mg tomivosertib without food (data from by eFFECTOR Therape…
View article: Supplementary Fig. S5 from Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer
Supplementary Fig. S5 from Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer Open
Supplementary Fig. S5: Translatomic profiling. Scatter plots demonstrating translation efficiency (TE) (top), Ribo-Seq (middle), RNA-Seq) (bottom) the fold change difference between ON MNKi and Pre-MNKi conditions for three different patie…
View article: Supplementary Table S4 from Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer
Supplementary Table S4 from Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer Open
Supplementary Table S4. (A) Investigator categorization of adverse events. (B) Overview of adverse events by CTCAE toxicity level.
View article: Supplementary Table S2 from Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer
Supplementary Table S2 from Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer Open
Supplementary Table S2. Representativeness of Study Participants.
View article: Supplementary Table S9 from Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer
Supplementary Table S9 from Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer Open
Supplementary Table S9: mRNAs affected by tomivosertib.
View article: Supplementary Fig. S4 from Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer
Supplementary Fig. S4 from Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer Open
Supplementary Fig. S4: Proteomic profiling. Heatmap showing the Normalized Enrichment Score (NES) for the main independent pathways enriched in at least 2 of the patients in the cohort.
View article: Supplementary Table S7 from Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer
Supplementary Table S7 from Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer Open
Supplementary Table S7: Phospho-eIF4E Immunohistochemistry. Results Demonstrating Changes in Phospho eIF4E From Baseline Biopsy for 14 Patients.
View article: Supplementary Fig. S2 from Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer
Supplementary Fig. S2 from Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer Open
Supplementary Fig. S2: Pharmacokinetic data. (A) Levels of Paclitaxel and Tomivosertib over time for 12 patients. During the run-in period (cycle 1) Tomivosertib was given as a single agent, so paclitaxel levels were undetectable. Tomivose…
View article: Supplementary Table S8 from Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer
Supplementary Table S8 from Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer Open
Supplementary Table S8: Protein changes by patient.
View article: Supplementary Table S5 from Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer
Supplementary Table S5 from Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer Open
Supplementary Table S5: Adverse events by CTCAE toxicity grade ≥ 3.
View article: Supplementary Fig. S9 from Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer
Supplementary Fig. S9 from Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer Open
Supplementary Fig. S9: Imaging mass cytometry. (A) Heatmap of signaling markers expression within cell clusters and (B) Neighbourhood analysis showing cell-to-cell interactions over all patients before and after treatment with tomivosertib.
View article: Supplementary Table S3 from Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer
Supplementary Table S3 from Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer Open
Supplementary Table S3: Prior treatments. Summary of breast cancer surgery, radiation therapy, and systemic anti-cancer therapy.
View article: Supplementary Fig. S8 from Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer
Supplementary Fig. S8 from Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer Open
Supplementary Fig. S8: Imaging mass cytometry. (A) Representative images showing marker expression used for our classification. (B) Proportion of immune clusters defined by IMC per patient.
View article: Supplementary Table S6 from Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer
Supplementary Table S6 from Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer Open
Supplementary Table S6: Summary of all adverse events.
View article: Supplementary Fig. S6 from Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer
Supplementary Fig. S6 from Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer Open
Supplementary Fig. S6: Translatomic profiling. UpSet plots display overlap of the translationally downregulated (A) and upregulated (B) mRNAs between each patient. The numbers above the bars represent the number of mRNAs that exclusively b…
View article: Data from Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer
Data from Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer Open
Purpose:Preclinical data motivate clinical evaluation of inhibitors of MAPK-interacting kinases 1 and 2 (MNK1/2). We conducted a phase 1b clinical trial to study target engagement and safety of tomivosertib, a MNK1/2 inhibitor, alone and i…
View article: Supplementary Fig. S7 from Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer
Supplementary Fig. S7 from Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer Open
Supplementary Fig. S7: Translatomic profiling. (A) Pairwise correlation among patients for changes in Ribo-seq level after tomivosertib treatment. r denotes Pearson’s correlation coefficient. (B) Heatmap plot and Euclidean distance hierarc…
View article: Proteomic profiling identifies muscle-invasive bladder cancers with distinct biology and responses to platinum-based chemotherapy
Proteomic profiling identifies muscle-invasive bladder cancers with distinct biology and responses to platinum-based chemotherapy Open
Platinum-based neoadjuvant chemotherapy prior to radical cystectomy is the preferred treatment for muscle-invasive bladder cancer despite modest survival benefit and significant associated toxicities. Here, we profile the global proteome o…
View article: Data Independent Acquisition to Inform the Development of Targeted Proteomics Assays Using a Triple Quadrupole Mass Spectrometer
Data Independent Acquisition to Inform the Development of Targeted Proteomics Assays Using a Triple Quadrupole Mass Spectrometer Open
Mass spectrometry based targeted proteomics methods provide sensitive and high-throughput analysis of selected proteins. To develop a targeted bottom-up proteomics assay, peptides must be evaluated as proxies for the measurement of a prote…
View article: Proteomic profiling identifies muscle-invasive bladder cancers with distinct biology and responses to platinum-based chemotherapy
Proteomic profiling identifies muscle-invasive bladder cancers with distinct biology and responses to platinum-based chemotherapy Open
Platinum-based neoadjuvant chemotherapy (NAC) prior to radical cystectomy is the preferred treatment for muscle-invasive bladder cancer (MIBC) despite modest survival benefit and significant associated toxicities. Here, we profiled the glo…