TRAIL therapy and prospective developments for cancer treatment

Thapa, Bindu; Kc, Remant Bahadur; Uludağ, Hasan

doi:10.1016/j.jconrel.2020.07.013

Cited by 58 publications

(39 citation statements)

References 179 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Fisetin also promoted therapeutic potential in the xenograft model generated from HDAC inhibitor-resistant cells [141]. Further, TRAIL is an immune cytokine of the TNF family that received attention as a targeted anti-cancer agent through the selective induction of apoptosis in cancer cells [143,144]. Despite tumor TRAIL's potential as a potent anticancer agent inducing apoptosis of cancer but not normal cells, colon cancer is often TRAIL-resistant.…”

Section: Flavonoids Enhance Effectiveness Of Targeted Anti-cancer Therapymentioning

confidence: 99%

Flavonoids as an effective sensitizer for anti-cancer therapy: insights into multi-faceted mechanisms and applicability towards individualized patient profiles

et al. 2021

View full text Add to dashboard Cite

Cost-efficacy of currently applied treatments is an issue in overall cancer management challenging healthcare and causing tremendous economic burden to societies around the world. Consequently, complex treatment models presenting concepts of predictive diagnostics followed by targeted prevention and treatments tailored to the personal patient profiles earn global appreciation as benefiting the patient, healthcare economy, and the society at large. In this context, application of flavonoids as a spectrum of compounds and their nano-technologically created derivatives is extensively under consideration, due to their multi-faceted anti-cancer effects applicable to the overall cost-effective cancer management, primary, secondary, and even tertiary prevention. This article analyzes most recently updated data focused on the potent capacity of flavonoids to promote anti-cancer therapeutic effects and interprets all the collected research achievements in the frame-work of predictive, preventive, and personalized (3P) medicine. Main pillars considered are:- Predictable anti-neoplastic, immune-modulating, drug-sensitizing effects;- Targeted molecular pathways to improve therapeutic outcomes by increasing sensitivity of cancer cells and reversing their resistance towards currently applied therapeutic modalities.

show abstract

Section: Flavonoids Enhance Effectiveness Of Targeted Anti-cancer Therapymentioning

confidence: 99%

Flavonoids as an effective sensitizer for anti-cancer therapy: insights into multi-faceted mechanisms and applicability towards individualized patient profiles

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Consequently, DR5 is considered a promising target for melanoma therapy. Since discovering the specific responsiveness of cancerous cells to TRAIL-mediated apoptosis, several TRAIL-based agents, such as recombinant human-soluble TRAIL (rhTRAIL), have been developed and tested in preclinical studies and clinical trials . However, no convincing therapeutical outcome of rhTRAIL was obtained in cancer patients because of its short half-life, insufficient targetability, and poor bioavailability .…”

Section: Introductionmentioning

confidence: 99%

“…However, no convincing therapeutical outcome of rhTRAIL was obtained in cancer patients because of its short half-life, insufficient targetability, and poor bioavailability . To overcome these drawbacks, drug-delivery vehicles such as liposome-based nanoparticles (NPs) and inorganic NPs have been developed . However, these vehicles cannot transform the total potentiality of TRAIL-based agents into clinically applicable productions.…”

Section: Introductionmentioning

confidence: 99%

Engineering Exosomes Endowed with Targeted Delivery of Triptolide for Malignant Melanoma Therapy

Jiang

et al. 2021

ACS Appl. Mater. Interfaces

View full text Add to dashboard Cite

Malignant melanoma is considered the most aggressive skin carcinoma with invasive growth patterns. Triptolide (TPL) possesses various biological and pharmacological activities involved in cancer treatment. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can induce cancer cell apoptosis by binding to DR5 highly expressed on cancer cells. Exosomes are natural nanomaterials with low immunogenicity, nontoxicity, and excellent biocompatibility and have been extensively used as emerging delivery vectors for diverse therapeutic cargos. Herein, a delivery system based on TRAIL-engineered exosomes (TRAIL-Exo) for loading TPL for targeted therapy against malignant melanoma is proposed and systematically investigated. Our results showed that TRAIL-Exo/TPL could improve tumor targetability, enhance cellular uptake, inhibit proliferation, invasion, and migration, and induce apoptosis of A375 cells through activating the extrinsic TRAIL pathway and the intrinsic mitochondrial pathway in vitro. Moreover, intravenous injection of TRAIL-Exo/TPL significantly suppressed tumor progression and reduced the toxicity of TPL in the melanoma nude mouse model. Together, our research presents a novel strategy for high-efficiency exosome-based drug-delivery nanocarriers and provides an alternative dimension for developing a promising approach with synergistic therapeutic efficacy and targeting capacity for melanoma treatment.

show abstract

Section: Introductionmentioning

confidence: 99%

“…However, TRAIL analogs and DR4/5 agonistic antibodies have yet to be clinically approved for anticancer therapy. This is due in part to pharmacokinetic issues related to these protein drugs themselves, and in part to the ability of cancer cells to acquire resistance through a variety of mechanisms, including downregulation of DR4 and DR5 (reviewed in [9]). Since DDAs upregulate DR5 and activate DR4 and DR5 in a ligandindependent manner [4,10], DDAs may overcome the resistance mechanisms that suppress the efficacy of other activators of the TRAIL/Death Receptor pathway.…”

Section: Introductionmentioning

confidence: 99%

Inhibitors of ERp44, PDIA1, and AGR2 induce disulfide-mediated oligomerization of Death Receptors 4 and 5 and cancer cell death

Law

Yaaghubi

Ghilardi

et al. 2021

Preprint

View full text Add to dashboard Cite

Breast cancer mortality remains unacceptably high, indicating a need for safer and more effective therapeutic agents. Disulfide bond Disrupting Agents (DDAs) were previously identified as a novel class of anticancer compounds that selectively kill cancers that overexpress the Epidermal Growth Factor Receptor (EGFR) or its family member HER2. DDAs kill EGFR+ and HER2+ cancer cells via the parallel downregulation of EGFR, HER2, and HER3 and activation/oligomerization of Death Receptors 4 and 5 (DR4/5). However, the mechanisms by which DDAs mediate these effects are unknown. Affinity purification analyses employing biotinylated-DDAs reveal that the Protein Disulfide Isomerase (PDI) family members AGR2, AGR3, PDIA1, and ERp44 are DDA target proteins. Further analyses demonstrate that shRNA-mediated knockdown of AGR2 and ERp44, or expression of ERp44 mutants, enhance basal and DDA-induced DR5 oligomerization. DDA treatment of breast cancer cells disrupts PDIA1 and ERp44 mixed disulfide bonds with their client proteins. Together, these results reveal DDAs as the first small molecule, active site inhibitors of AGR2 and ERp44, demonstrate a role for AGR2 and ERp44 in regulating the activity, stability, and localization of DR4 and DR5, and nominate ERp44 as a new molecular target for anticancer therapeutics.

show abstract

TRAIL therapy and prospective developments for cancer treatment

Cited by 58 publications

References 179 publications

Flavonoids as an effective sensitizer for anti-cancer therapy: insights into multi-faceted mechanisms and applicability towards individualized patient profiles

Flavonoids as an effective sensitizer for anti-cancer therapy: insights into multi-faceted mechanisms and applicability towards individualized patient profiles

Engineering Exosomes Endowed with Targeted Delivery of Triptolide for Malignant Melanoma Therapy

Inhibitors of ERp44, PDIA1, and AGR2 induce disulfide-mediated oligomerization of Death Receptors 4 and 5 and cancer cell death

Contact Info

Product

Resources

About