ArticleClinical cancer research : an official journal of the American Association for Cancer Research2012
Elevation of c-FLIP in castrate-resistant prostate cancer antagonizes therapeutic response to androgen receptor-targeted therapy.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 68 citations in OpenAlex.
- Inhibition of c-FLIP alongside TRAIL treatment suppresses prostate cancer stem cell activity.British journal of cancer · 2026Article
- c-FLIP as a master regulator of immune homeostasis and disease mechanisms.Cell death & disease · 2026Review
- The interconnection between androgen receptor and DNA damage response pathways in prostate cancer.Current urology · 2025Review
- How does caspases regulation play role in cell decisions? apoptosis and beyond.Molecular and cellular biochemistry · 2024Review
- Bortezomib in Combination with Physachenolide C Reduces the Tumorigenic Properties of KRASCancers · 2024Article
- The role of histone post-translational modifications in cancer and cancer immunity: functions, mechanisms and therapeutic implications.Frontiers in immunology · 2024Review
- c-FLIP promotes drug resistance in non-small-cell lung cancer cells via upregulating FoxM1 expression.Acta pharmacologica Sinica · 2022Article
- Attenuating Adaptive VEGF-A and IL8 Signaling Restores Durable Tumor Control in AR Antagonist-Treated Prostate Cancers.Molecular cancer research : MCR · 2022Article
- Interaction between the Hepatitis B Virus and Cellular FLIP Variants in Viral Replication and the Innate Immune System.Viruses · 2022Review
- Estrogen Receptors-Mediated Apoptosis in Hormone-Dependent Cancers.International journal of molecular sciences · 2022Review
- Non-apoptotic function of caspase-8 confers prostate cancer enzalutamide resistance via NF-κB activation.Cell death & disease · 2021Article
- Cut-like homeobox 1 (CUX1) tumor suppressor gene haploinsufficiency induces apoptosis evasion to sustain myeloid leukemia.Nature communications · 2021Article
- Resistance to Antiandrogens in Prostate Cancer: Is It Inevitable, Intrinsic or Induced?Cancers · 2021Review
- TRAIL of Hope Meeting Resistance in Cancer.Trends in cancer · 2020Review
- Hypo-Expression of Flice-Inhibitory Protein and Activation of the Caspase-8 Apoptotic Pathways in the Death-Inducing Signaling Complex Due to Ischemia Induced by the Compression of the Asphyxiogenic Tool on the Skin in Hanging Cases.Diagnostics (Basel, Switzerland) · 2020Article
- DR5-targeted, chemotherapeutic drug-loaded nanoparticles induce apoptosis and tumor regression in pancreatic cancer in vivo models.Journal of controlled release : official journal of the Controlled Release Society · 2020Article
- A revised model of TRAIL-R2 DISC assembly explains how FLIP(L) can inhibit or promote apoptosis.EMBO reports · 2020Article
- miR-125b suppresses cellular proliferation by targeting c-FLIP in gallbladder carcinoma.Oncology letters · 2019Article
- Review
- Chemical screen for epigenetic barriers to single allele activation of Oct4.Stem cell research · 2019Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
purposeTo characterize the importance of cellular Fas-associated death domain (FADD)-like interleukin 1β-converting enzyme (FLICE) inhibitory protein (c-FLIP), a key regulator of caspase-8 (FLICE)-promoted apoptosis, in modulating the response of prostate cancer cells to androgen receptor (AR)-targeted therapy. EXPERIMENTAL
designc-FLIP expression was characterized by immunohistochemical analysis of prostatectomy tissue. The functional importance of c-FLIP to survival and modulating response to bicalutamide was studied by molecular and pharmacologic interventions.
resultsc-FLIP expression was increased in high-grade prostatic intraepithelial neoplasia and prostate cancer tissue relative to normal prostate epithelium (P < 0.001). Maximal c-FLIP expression was detected in castrate-resistant prostate cancer (CRPC; P < 0.001). In vitro, silencing of c-FLIP induced spontaneous apoptosis and increased 22Rv1 and LNCaP cell sensitivity to bicalutamide, determined by flow cytometry, PARP cleavage, and caspase activity assays. The histone deacetylase inhibitors (HDACi), droxinostat and SAHA, also downregulated c-FLIP expression, induced caspase-8- and caspase-3/7-mediated apoptosis, and increased apoptosis in bicalutamide-treated cells. Conversely, the elevated expression of c-FLIP detected in the CRPC cell line VCaP underpinned their insensitivity to bicalutamide and SAHA in vitro. However, knockdown of c-FLIP induced spontaneous apoptosis in VCaP cells, indicating its relevance to cell survival and therapeutic resistance.
conclusionc-FLIP reduces the efficacy of AR-targeted therapy and maintains the viability of prostate cancer cells. A combination of HDACi with androgen deprivation therapy may be effective in early-stage disease, using c-FLIP expression as a predictive biomarker of sensitivity. Direct targeting of c-FLIP, however, may be relevant to enhance the response of existing and novel therapeutics in CRPC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.