A5024158066- Prostate Cancer Treatment and Research
- Histone Deacetylase Inhibitors Research
- Cancer, Hypoxia, and Metabolism
- Protein Degradation and Inhibitors
- Estrogen and related hormone effects
- Ubiquitin and proteasome pathways
- Cancer, Lipids, and Metabolism
- Radiopharmaceutical Chemistry and Applications
- Peptidase Inhibition and Analysis
- Advanced Breast Cancer Therapies
- Cancer Genomics and Diagnostics
- Glioma Diagnosis and Treatment
- Ferroptosis and cancer prognosis
- Cancer Immunotherapy and Biomarkers
- Chromatin Remodeling and Cancer
- PARP inhibition in cancer therapy
- Epigenetics and DNA Methylation
- Neuroblastoma Research and Treatments
- Cancer-related gene regulation
- Melanoma and MAPK Pathways
- Cancer-related Molecular Pathways
- Mass Spectrometry Techniques and Applications
Fred Hutch Cancer Center
2019-2023
Abstract The increased treatment of metastatic castration-resistant prostate cancer (mCRPC) with second-generation antiandrogen therapies (ADT) has coincided a greater incidence lethal, aggressive variant (AVPC) tumors that have lost dependence on androgen receptor (AR) signaling. These AR-independent may also transdifferentiate to express neuroendocrine lineage markers and are termed (NEPC). Recent evidence suggests kinase signaling be an important driver NEPC. To identify targetable...
Castration-resistant prostate cancer (CRPC) consists of multiple phenotypic subtypes including androgen receptor (AR)-active (ARPC) and neuroendocrine (NEPC). Tumor cells with these phenotypes can coexist between metastases within a patient an individual tumor. Treatments that are effective across CRPC currently lacking. Histone deacetylation is crucial for the regulation chromatin structure maintenance cell state activation PI3K/AKT/mTOR signaling cascade tumor growth-promoting pathway. We...
Introduction Brain tumors are the most common solid malignancy and leading cause of cancer-related deaths in infants. Current epidemiological data is limited by low numbers reported cases. This study used a population-based approach with analysis contemporary historical survival curves to provide up-to-date prognostication. Methods Observational cohort was performed using Surveillance, Epidemiology End Results (SEER) database. Infants brain diagnosed from 1973 2013 were categorized tumor...
Abstract Increased treatment of metastatic castration resistant prostate cancer (mCRPC) with second-generation anti-androgen therapies (ADT) has coincided a greater incidence lethal, aggressive variant (AVPC) tumors that have lost androgen receptor (AR) signaling. AVPC may also express neuroendocrine markers, termed (NEPC). Recent evidence suggests kinase signaling be an important driver NEPC. To identify targetable kinases in NEPC, we performed global phosphoproteomics comparing AR-negative...
<div>Abstract<p>The increased treatment of metastatic castration-resistant prostate cancer (mCRPC) with second-generation antiandrogen therapies (ADT) has coincided a greater incidence lethal, aggressive variant (AVPC) tumors that have lost dependence on androgen receptor (AR) signaling. These AR-independent may also transdifferentiate to express neuroendocrine lineage markers and are termed (NEPC). Recent evidence suggests kinase signaling be an important driver NEPC. To...
<p>Supplemental Figure 1. RET expression is higher in prostate cancer lines that have lost androgen receptor signaling Supplemental 2. gene patient samples with pure/mixed small cell phenotype or primary NEPC and correlates other neuroendocrine markers. 3. Knockdown of kinase PC3 cells shows a modest reduction cellular proliferation. 4. Prostate show variable sensitivity to inhibitor treatment. 5. Organoids derived from PTEN-/- Rb-/- model multiple aspects including resistance...
<div>Abstract<p>The increased treatment of metastatic castration-resistant prostate cancer (mCRPC) with second-generation antiandrogen therapies (ADT) has coincided a greater incidence lethal, aggressive variant (AVPC) tumors that have lost dependence on androgen receptor (AR) signaling. These AR-independent may also transdifferentiate to express neuroendocrine lineage markers and are termed (NEPC). Recent evidence suggests kinase signaling be an important driver NEPC. To...
<p>Supplemental Figure 1. RET expression is higher in prostate cancer lines that have lost androgen receptor signaling Supplemental 2. gene patient samples with pure/mixed small cell phenotype or primary NEPC and correlates other neuroendocrine markers. 3. Knockdown of kinase PC3 cells shows a modest reduction cellular proliferation. 4. Prostate show variable sensitivity to inhibitor treatment. 5. Organoids derived from PTEN-/- Rb-/- model multiple aspects including resistance...
<p>Supplementary Figure 8. Fimepinostat treatment of NEPC tumors is associated with tumor growth inhibition, apoptosis, and diminished ASCL1 expression.</p>
<p>Supplementary Figure 6. Fimepinostat treatment of prostate adenocarcinoma tissue slices causes growth inhibition and AR Myc.</p>
<p>Supplementary Figure 2. Effects of HDAC inhibitors on AR and Myc expression in prostate cancer cell lines.</p>
<p>Supplementary Figure 9. Romidepsin demonstrates broad activity across prostate cancer models with preferential potency in NEPC.</p>
<p>Supplementary Figure 17. Pathway analysis of hallmark (A) and KEGG (B) genes from C4-2B NCI-H660 cells treated with vehicle, fimepinostat, ipatasertib, romidepsin, or a combination ipatasertib + romidepsin.</p>
<p>Supplementary Figure 6. Fimepinostat treatment of prostate adenocarcinoma tissue slices causes growth inhibition and AR Myc.</p>
<p>Supplementary Figure 16. Overlapping gene expression in C4-2B and NCI-H660 cells treated with vehicle, fimepinostat, ipatasertib, romidepsin, or a combination of ipatasertib + romidepsin.</p>
<p>Supplementary Figure 9. Romidepsin demonstrates broad activity across prostate cancer models with preferential potency in NEPC.</p>
<p>Supplementary Figure 15. RNA-seq volcano plots of C4-2B and NCI-H660 cells treated with vehicle, fimepinostat, ipatasertib, romidepsin, or a combination ispatasertib + romidepsin.</p>
<p>Supplementary Figure 4. Enforced expression of AR-FL, Myc, or activated AKT1 does not rescue the growth inhibitory effects fimepinostat therapy.</p>
<p>Supplementary Figure 7. Mouse body weights with fimepinostat or romidepsin therapy.</p>