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The Journal of Urology Jul 2023
Topics: Humans; Gemcitabine; Docetaxel; Urinary Bladder Neoplasms; Deoxycytidine; Administration, Intravesical; Neoplasm Invasiveness; BCG Vaccine
PubMed: 37000006
DOI: 10.1097/JU.0000000000003438 -
Expert Opinion on Drug Delivery Mar 2019Docetaxel (DTX) is one of the most important chemotherapeutic agents and has been widely used for treatment of various types of cancers. However, the clinical... (Review)
Review
INTRODUCTION
Docetaxel (DTX) is one of the most important chemotherapeutic agents and has been widely used for treatment of various types of cancers. However, the clinical chemotherapy of DTX gives many undesirable side effects due to the usage of organic solvent in the injection and its low selectivity for tumor cells. With the evolution of pharmaceutical technologies, great efforts have been paid to develop new DTX formulations to overcome these problems.
AREAS COVERED
This review provided an overview of the preparation and activities of new DTX formulations, which were classified by administration methods, including injection, oral, transdermal and rectal administration. Besides, up to date information of the clinical status of new DTX formulations was summarized. We also discussed the challenges and perspectives of the future development of DTX formulations.
EXPERT OPINION
There have been numerous studies on new DTX-based formulations in recent years, and many of them exhibited significantly enhanced anti-tumor and targeting activity compared with DTX in preclinical studies. However, only a few entered clinical trials, and none has been approved into market. The clinical translation of experimental drug faces many hurdles, including the limited knowledge of nanomedicine and oncology, safety issues, controllable and reproducible production.
Topics: Animals; Antineoplastic Agents; Docetaxel; Drug Compounding; Humans; Nanomedicine; Nanoparticles; Neoplasms; Technology, Pharmaceutical
PubMed: 30773947
DOI: 10.1080/17425247.2019.1583644 -
Drug Delivery Dec 2022To realize the synergistic anti-tumor effect of chemotherapy and photodynamic therapy, the mono sulfide-modified docetaxel (DTX) prodrugs (DSD) provided by our...
To realize the synergistic anti-tumor effect of chemotherapy and photodynamic therapy, the mono sulfide-modified docetaxel (DTX) prodrugs (DSD) provided by our laboratory and hematoporphyrin (HP) were used to physically prepare co-assembled nanoparticles (DSD/HP NPs) by nano-precipitation. For the first time, this study showed its characteristics, anti-tumor activity, pharmacokinetic behavior in rats, distribution, and pharmacodynamic effects on 4T1 tumor-bearing Bal b/c mice. DSD/HP NPs optimized by single-factor and response surface optimization had several distinct characteristics. First, it had dark purple appearance with particle size of 105.16 ± 1.24 nm, PDI of 0.168 ± 0.15, entrapment efficiency and drug loading of DSD and HP in DSD/HP NPs of 96.27 ± 1.03% and 97.70 ± 0.20%, 69.22 ± 1.03% and 20.03 ± 3.12%, respectively. Second, it had good stability and could release DTX and HP slowly in the media of pH 7.4 PBS with 10 mM DTT (HO). Moreover, DSD/HP NPs along with NiR treatment significantly inhibited 4T1 cells proliferation, and induced more reactive oxygen species and cells apoptosis. pharmacokinetic and pharmacodynamic studies showed that DSD/HP NPs could prolong the drug circulation time in rats, increase drug distribution in tumor site, obviously inhibit tumor growth, and decrease the exposure of drug to normal tissues. Therefore, DSD/HP NPs as a promising co-assembled nano-drug delivery system could potentially improve the therapeutic efficiency of chemotherapeutic drug and achieve better anti-tumor effects due to the combination of chemotherapy and photodynamic therapy.
Topics: Rats; Mice; Animals; Hematoporphyrins; Docetaxel; Photochemotherapy; Prodrugs; Hydrogen Peroxide; Drug Carriers; Nanoparticles; Neoplasms
PubMed: 36397301
DOI: 10.1080/10717544.2022.2147280 -
Bioorganic Chemistry Aug 2023Herein, atropisomeric 8-aryltetrahydroisoquinolines have been synthesized and biologically evaluated. Based on our structure-activity relationship study, a highly...
Herein, atropisomeric 8-aryltetrahydroisoquinolines have been synthesized and biologically evaluated. Based on our structure-activity relationship study, a highly bioactive racemic compound has been produced, and it exhibited high antiproliferative activities against various cancer cell lines, including docetaxel-resistant breast cancer cell lines. Each enantiomer can be synthesized in an enantioselective manner by employing the chiral phosphoric acid-catalyzed atroposelective Pictet-Spengler cyclization. An axially (R)-configured enantiomer showed a higher biological activity compared with the axially (S)-configured enantiomer. Further biological studies suggested that the (R)-enantiomer overcomes docetaxel resistance via the downregulation of signal transducer and activator of transcription 3 activation and consequently induces cellular apoptosis in docetaxel-resistant triple-negative breast cancer cell lines.
Topics: Humans; Docetaxel; Tetrahydroisoquinolines; Triple Negative Breast Neoplasms; Apoptosis; Cell Line, Tumor
PubMed: 37229969
DOI: 10.1016/j.bioorg.2023.106573 -
Practical Radiation Oncology 2023
Prostate Stereotactic Body Radiation Therapy Margins, Accelerated Partial Breast Irradiation Techniques, Total Neoadjuvant Therapy Local Control, Hyperfractionated Reirradiation, Hyaluronic Acid Rectal Spacer, and Concurrent Docetaxel for Head and Neck Cancer.
Topics: Male; Humans; Docetaxel; Prostate; Re-Irradiation; Hyaluronic Acid; Neoadjuvant Therapy; Head and Neck Neoplasms; Breast Neoplasms
PubMed: 37391233
DOI: 10.1016/j.prro.2023.04.005 -
Advanced Science (Weinheim,... Dec 2021Increasing evidence has suggested that chemotherapeutics affect the integrity of the intestinal barrier and alter the intestinal microbiota, thus limiting the...
Increasing evidence has suggested that chemotherapeutics affect the integrity of the intestinal barrier and alter the intestinal microbiota, thus limiting the therapeutic outcomes of cancer chemotherapy. Docetaxel (DTX) is used for breast cancer treatment and has gastrointestinal side effects, but the influence of DTX formulations on the intestinal barrier and intestinal microbiota remains unknown. Therefore, in this work, the influence of DTX injection (free DTX, commercial formulation) and DTX/methoxy poly(ethylene glycol)-block-poly(D,L-lactide) (mPEG-PDLLA) (DTX micelles, nanoformulation) on the integrity of the intestinal barrier and the intestinal microbiota is investigated. It is found that the free DTX causes significantly greater intestinal barrier damage than the DTX micelles. The diversity of the intestinal microbiota, and the relative abundance of Akkermansia muciniphila and Ruminococcus gnavus in the DTX micelle-treated group is significantly higher than that in the free DTX-treated group. Moreover, the tumor growth rate is elevated in antibiotic mixture-pretreated mice, demonstrating that the diversity and composition of the intestinal microbiota may be associated with tumor progression. This work demonstrates that different formulations of chemotherapeutics have different effects on the integrity of the intestinal barrier and the intestinal microbiota.
Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Caco-2 Cells; Colorectal Neoplasms; Disease Models, Animal; Docetaxel; Female; Gastrointestinal Microbiome; Humans; Intestinal Mucosa; Mice; Mice, Inbred BALB C; Micelles
PubMed: 34713626
DOI: 10.1002/advs.202102952 -
Drug Resistance Updates : Reviews and... Mar 2024This study aims to explore the function and mechanism of G Protein-coupled receptor class C group 5 member A (GPRC5A) in docetaxel-resistance and liver metastasis of...
AIMS
This study aims to explore the function and mechanism of G Protein-coupled receptor class C group 5 member A (GPRC5A) in docetaxel-resistance and liver metastasis of breast cancer.
METHODS
Single-cell RNA transcriptomic analysis and bioinformatic analysis are used to screen relevant genes in breast cancer metastatic hepatic specimens. MeRIP, dual-luciferase analysis and bioinformation were used to detect m6A modulation. Mass spectrometry (MS), co-inmunoprecipitation (co-IP) and immunofluorescence colocalization were executed to explore the mechanism of GPRC5A in breast cancer cells.
RESULT
GPRC5A was upregulated in triple-negative breast cancer (TNBC) and was associated with a poor prognosis. In vitro and in vivo experiments demonstrated that knockdown of GPRC5A alleviated metastasis and resistance to docetaxel in TNBC. Overexpression of GPRC5A had the opposite effects. The m6A methylation of GPRC5A mRNA was modulated by METTL3 and YTHDF1, which facilitates its translation. GPRC5A inhibited the ubiquitination-dependent degradation of LAMTOR1, resulting in the recruitment of mTORC1 to lysosomes and activating the mTORC1/p70s6k signaling pathway.
CONCLUSION
METTL3/YTHDF1 axis up-regulates GPRC5A expression by m6A methylation. GPRC5A activates mTORC1/p70s6k signaling pathway by recruiting mTORC1 to lysosomes, consequently promotes docetaxel-resistance and liver metastasis.
Topics: Humans; Docetaxel; Triple Negative Breast Neoplasms; Ribosomal Protein S6 Kinases, 70-kDa; Signal Transduction; Methylation; Liver Neoplasms; Receptors, G-Protein-Coupled; TOR Serine-Threonine Kinases; Mechanistic Target of Rapamycin Complex 1; Methyltransferases
PubMed: 38335844
DOI: 10.1016/j.drup.2024.101063 -
Cell Communication and Signaling : CCS Dec 2022Tumor glycolysis is a critical event for tumor progression. Docetaxel is widely used as a first-line drug for chemotherapy and shown to have a survival advantage....
BACKGROUND
Tumor glycolysis is a critical event for tumor progression. Docetaxel is widely used as a first-line drug for chemotherapy and shown to have a survival advantage. However, the role of docetaxel in tumor glycolysis remained poorly understood.
METHODS
The effect of Docetaxel in tumor glycolysis and proliferation were performed by CCK-8, Western blotting, real-time PCR, glucose, and lactate detection and IHC. ChIP and luciferase assay were used to analyze the mechanism of Docetaxel on Smad3-mediated HIF-1α transactivity.
RESULTS
In this study, we showed that docetaxel treatment led to a significant inhibition of cell proliferation in prostate cancer cells through PFKP-mediated glycolysis. Addition of lactate, a production of glycolysis, could reverse the inhibitory effect of docetaxel on cell proliferation. Further analysis has demonstrated that phosphorylation of Smad3 (Ser213) was drastically decreased in response to docetaxel stimulation, leading to reduce Smad3 nuclear translocation. Luciferase and Chromatin immunoprecipitation (ChIP) analysis revealed that docetaxel treatment inhibited the binding of Smad3 to the promoter of the HIF-1α gene, suppressing transcriptional activation of HIF-1α. Moreover, ectopic expression of Smad3 in prostate cancer cells could overcome the decreased HIF-1α expression and its target gene PFKP caused by docetaxel treatment. Most importantly, endogenous Smad3 regulated and interacted with HIF-1α, and this interaction was destroyed in response to docetaxel treatment. What's more, both HIF-1α and PFKP expression were significantly reduced in prostate cancer received docetaxel treatment in vivo.
CONCLUSION
These findings extended the essential role of docetaxel and revealed that docetaxel inhibited cell proliferation by targeting Smad3/HIF-1α signaling-mediated tumor Warburg in prostate cancer cells. Video Abstract.
Topics: Male; Humans; Docetaxel; Cell Line, Tumor; Prostatic Neoplasms; Cell Proliferation; Glycolysis; Luciferases; Hypoxia-Inducible Factor 1, alpha Subunit; Smad3 Protein
PubMed: 36536346
DOI: 10.1186/s12964-022-00950-z -
Cancer Medicine Aug 2023This study examined the health-related quality of life (HRQoL) of patients with advanced non-small cell lung cancer (NSCLC) receiving tislelizumab versus docetaxel in... (Randomized Controlled Trial)
Randomized Controlled Trial
This study examined the health-related quality of life (HRQoL) of patients with advanced non-small cell lung cancer (NSCLC) receiving tislelizumab versus docetaxel in the open-label, multicenter, Phase 3 trial called RATIONALE-303 (NCT03358875). HRQoL was assessed with the EORTC QLQ-C30, EORTC QLQ-LC13, and the EQ-5D-5L instruments. A longitudinal analysis of covariance assessed the change from baseline to Week 12 and from baseline to Week 18. A time to deterioration analysis was also performed using the Kaplan-Meier method. Eight hundred and five patients were randomized to either tislelizumab (n = 535) or docetaxel, respectively (535 and 270 to tislelizumab and docetaxel, respectively). The tislelizumab arm improved while the docetaxel arm worsened in the QLQ-C30 global health status/QoL scale score (difference LS mean change Week 18: 5.7 [95% CI: 2.38, 9.07, p = 0.0008]), fatigue (Week 12: -3.2 [95% CI: -5.95, -0.37, p < 0.0266]; Week 18: -4.9 [95% CI: -8.26, -1.61, p = 0.0037]), and QLQ-LC13 symptom index score (Week 12: -5.5 [95% CI: -6.93, -4.04, P < 0.0001]; Week 18: -6.6 [95% CI: -8.25, -4.95, p < 0.0001]). The tislelizumab arm had improvements in coughing versus the docetaxel arm (Week 12: -4.7 [95% CI: -8.57, -0.78, p = 0.0188]; Week 18: -8.3 [95% CI: -13.02, -3.51, p = 0.0007]). The patients who received tislelizumab were less at risk for clinically meaningful worsening in the overall lung cancer symptom index scale (hazard ratio (HR): 0.24 [95% CI: 0.162, 0.356], p < 0.0001), dyspnea (HR: 0.74 [95% CI: 0.567, 0.958], p = 0.0109), coughing (HR: 0.74 [95% CI: 0.534, 1.019], p = 0.0309), and peripheral neuropathy (HR: 0.55 [95% CI: 0.370, 0.810] p = 0.0011). In general, tislelizumab versus docetaxel was associated with improved HRQoL and symptoms of lung cancer in patients who previously failed treatment with platinum-containing chemotherapy.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Quality of Life; Docetaxel; Cough
PubMed: 37587845
DOI: 10.1002/cam4.6361 -
JAMA Oncology Jun 2024Metastatic hormone-sensitive prostate cancer is currently an incurable disease. Despite a high response rate to androgen-deprivation therapy, most cases progress to... (Review)
Review
IMPORTANCE
Metastatic hormone-sensitive prostate cancer is currently an incurable disease. Despite a high response rate to androgen-deprivation therapy, most cases progress to castration-resistant disease, the terminal phase. This review provides a summary of the most recent evidence for current and emerging management strategies, including treatment intensification with combinations of therapies. It also provides recommendations on applying the evidence in clinical practice to encourage appropriate treatment to improve survival outcomes among patients with metastatic hormone-sensitive prostate cancer.
OBSERVATIONS
Androgen-deprivation therapy is the backbone of treatment for metastatic hormone-sensitive prostate cancer; however, it is insufficient alone to provide sustained disease control and long-term survival. Addition of an androgen receptor pathway inhibitor and/or docetaxel significantly improves survival, as demonstrated by several international phase 3 randomized clinical trials. Triplet therapy composed of androgen-deprivation therapy plus an androgen receptor pathway inhibitor plus docetaxel has been shown to improve overall survival over androgen-deprivation therapy plus docetaxel. In the ARASENS trial (darolutamide), the hazard ratios (HRs) were 0.68 (95% CI, 0.57-0.80) in the overall population; 0.71 (95% CI, 0.59-0.85) and 0.61 (95% CI, 0.35-1.05) in patients with de novo and recurrent disease, respectively; 0.69 (95% CI, 0.57-0.82) and 0.72 (95% CI, 0.41-1.13) in patients with high-volume and low-volume disease, respectively; and 0.71 (95% CI, 0.58-0.86) and 0.62 (95% CI, 0.42-0.90) in patients with high-risk and low-risk disease, respectively. In the PEACE-1 trial (abiraterone acetate + prednisone), the HRs were 0.75 (95% CI, 0.59-0.95; all de novo) in the overall population and 0.72 (95% CI, 0.55-0.95) and immature in the high-volume and low-volume subgroups, respectively. In the ENZAMET trial (enzalutamide), the HRs were 0.82 (95% CI, 0.63-1.06) in the overall population; 0.73 (95% CI, 0.55-0.99) and 1.10 (95% CI, 0.65-1.86) in the de novo and recurrent subgroups, respectively; and 0.87 (95% CI, 0.66-1.17) and 0.61 (95% CI, 0.33-1.10) in the high-volume and low-volume subgroups. Combination regimens are generally well tolerated, with adverse effects dependent on the profiles of the component drugs.
CONCLUSIONS AND RELEVANCE
The findings of this review show compelling evidence from phase 3 randomized clinical trials in favor of initiating triplet combination therapy for patients with metastatic hormone-sensitive prostate cancer for the best overall survival. Patients who are eligible for chemotherapy should be offered androgen-deprivation therapy plus an androgen receptor pathway inhibitor plus docetaxel, particularly patients with high-volume, high-risk, or de novo metastatic disease.
Topics: Humans; Male; Antineoplastic Combined Chemotherapy Protocols; Androgen Antagonists; Prostatic Neoplasms; Treatment Outcome; Neoplasm Metastasis; Androgen Receptor Antagonists; Docetaxel
PubMed: 38722620
DOI: 10.1001/jamaoncol.2024.0591