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Biomaterials May 2021The clinical application of taxane (including paclitaxel, docetaxel, and cabazitaxel)-based formulations is significantly impeded by their off-target distribution,... (Review)
Review
The clinical application of taxane (including paclitaxel, docetaxel, and cabazitaxel)-based formulations is significantly impeded by their off-target distribution, unsatisfactory release, and acquired resistance/metastasis. Recent decades have witnessed a dramatic progress in the development of high-efficiency, low-toxicity nanotaxanes via the use of novel biomaterials and nanoparticulate drug delivery systems (nano-DDSs). Thus, in this review, the achievements of nanotaxanes-targeted delivery and stimuli-responsive nano-DDSs-in preclinical or clinical trials have been outlined. Then, emerging nanotherapeutics against tumor resistance and metastasis have been overviewed, with a particular emphasis on synergistic therapy strategies (e.g., combination with surgery, chemotherapy, radiotherapy, biotherapy, immunotherapy, gas therapy, phototherapy, and multitherapy). Finally, the latest oral nanotaxanes have been briefly discussed.
Topics: Antineoplastic Agents; Docetaxel; Drug Delivery Systems; Humans; Immunotherapy; Neoplasms
PubMed: 33836293
DOI: 10.1016/j.biomaterials.2021.120790 -
Journal of Thoracic Oncology : Official... May 2019Data on immuno-oncology agents in Chinese patients are limited despite a need for new therapies. We evaluated the efficacy and safety of nivolumab in a predominantly... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Data on immuno-oncology agents in Chinese patients are limited despite a need for new therapies. We evaluated the efficacy and safety of nivolumab in a predominantly Chinese patient population with previously treated NSCLC.
METHODS
CheckMate 078 was a randomized, open-label, phase III clinical trial in patients from China, Russia, and Singapore with squamous or nonsquamous NSCLC that had progressed during/after platinum-based doublet chemotherapy (ClinicalTrials.gov: NCT02613507). Patients with EGFR/ALK alterations were excluded. Patients (N = 504) were randomized 2:1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m every 3 weeks), stratified by performance status, tumor histology, and tumor programmed death ligand 1 expression. The primary endpoint was overall survival (OS); secondary endpoints included objective response rate, progression-free survival, and safety.
RESULTS
OS was significantly improved with nivolumab (n = 338) versus docetaxel (n = 166); median OS (95% confidence interval): 12.0 (10.4-14.0) versus 9.6 (7.6-11.2) months, respectively; hazard ratio (97.7% confidence interval): 0.68 (0.52-0.90); p = 0.0006. Objective response rate was 17% with nivolumab versus 4% with docetaxel; median duration of response was not reached versus 5.3 months. Minimum follow-up was 8.8 months. The frequency of grade 3 or greater treatment-related adverse events was 10% with nivolumab and 48% with docetaxel.
CONCLUSIONS
This is the first phase III study in a predominantly Chinese population reporting results with a programmed death 1 inhibitor. In this population with previously treated advanced NSCLC, nivolumab improved OS versus docetaxel. Results were consistent with global CheckMate 017 and 057 studies.
Topics: Adult; Aged; Antineoplastic Agents, Immunological; Asian People; Carcinoma, Non-Small-Cell Lung; Docetaxel; Female; Humans; Lung Neoplasms; Male; Middle Aged; Nivolumab
PubMed: 30659987
DOI: 10.1016/j.jtho.2019.01.006 -
International Immunopharmacology Jun 2023There are several interactions within the tumor microenvironment (TME) that affect the response of cancer cells to therapy. There are also a large number of cells and... (Review)
Review
There are several interactions within the tumor microenvironment (TME) that affect the response of cancer cells to therapy. There are also a large number of cells and secretions in TME that increase resistance to therapy. Following the release of immunosuppressive, pro-angiogenic, and metastatic molecules by certain cells such as tumor-associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), and cancer cells, immune evasion, angiogenesis, and metastasis may be induced. However, natural killer (NK) cells and cytotoxic CD8 + T lymphocytes (CTLs) can responsively release anticancer molecules. In addition, anticancer drugs can modulate these cells and their interactions in favor of either cancer resistance or therapy. Docetaxel belongs to taxanes, a class of anti-tumor drugs, which acts through the polymerization of tubulin and the induction of cell cycle arrest. Also, it has been revealed that taxanes including docetaxel affect cancer cells and the other cells within TME through some other mechanisms such as modulation of immune system responses, angiogenesis, and metastasis. In this paper, we explain the basic mechanisms of docetaxel interactions with malignant cells. Besides, we review the diverse effects of docetaxel on TME and cancer cells in consequence. Lastly, the modulatory effects of docetaxel alone or in conjunction with other anticancer agents on anti-tumor immunity, cancer cell resistance, angiogenesis, and metastasis will be discussed.
Topics: Humans; Docetaxel; Tumor Microenvironment; Neoplasms; Antineoplastic Agents; T-Lymphocytes, Cytotoxic
PubMed: 37126985
DOI: 10.1016/j.intimp.2023.110214 -
Targeted Oncology Sep 2023Darolutamide (NUBEQA) is an oral androgen receptor inhibitor (ARi) that is approved for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC) in... (Review)
Review
Darolutamide (NUBEQA) is an oral androgen receptor inhibitor (ARi) that is approved for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC) in combination with androgen deprivation therapy (ADT) and docetaxel. In a pivotal trial, darolutamide plus ADT and docetaxel was superior to placebo plus ADT and docetaxel in prolonging the primary endpoint of overall survival, with improvements also reported in most secondary endpoints. Treatment with darolutamide plus ADT and docetaxel was associated with a manageable tolerability profile. Furthermore, the adverse events reported with darolutamide plus ADT and docetaxel were generally consistent with the safety profiles previously reported for ADT and docetaxel. Darolutamide expands the availability of treatment options in mHSPC and may be useful as a treatment for high-volume disease (typically defined as ≥ 4 bone metastases with spread outside of the pelvis and vertebral column).
Topics: Male; Humans; Prostatic Neoplasms; Docetaxel; Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Hormones
PubMed: 37542594
DOI: 10.1007/s11523-023-00984-4 -
Journal of Clinical Rheumatology :... Apr 2020
Topics: Aged; Biopsy; Breast Neoplasms; Docetaxel; Female; Humans; Magnetic Resonance Imaging; Muscles; Myositis; Taxoids
PubMed: 30148754
DOI: 10.1097/RHU.0000000000000888 -
Scientific Reports Jun 2023Enzalutamide, docetaxel, and cabazitaxel treatment resistance is a major problem in metastatic castration resistant prostate cancer (mCRPC), but the underlying genetic...
Enzalutamide, docetaxel, and cabazitaxel treatment resistance is a major problem in metastatic castration resistant prostate cancer (mCRPC), but the underlying genetic determinants are poorly understood. To identify genes that modulate treatment response to these drugs, we performed three genome-wide CRISPR/Cas9 knockout screens in the mCRPC cell line C4. The screens identified seven candidates for enzalutamide (BCL2L13, CEP135, E2F4, IP6K2, KDM6A, SMS, and XPO4), four candidates for docetaxel (DRG1, LMO7, NCOA2, and ZNF268), and nine candidates for cabazitaxel (ARHGAP11B, DRG1, FKBP5, FRYL, PRKAB1, RP2, SMPD2, TCEA2, and ZNF585B). We generated single-gene C4 knockout clones/populations for all genes and could validate effect on treatment response for five genes (IP6K2, XPO4, DRG1, PRKAB1, and RP2). Altered enzalutamide response upon IP6K2 and XPO4 knockout was associated with deregulation of AR, mTORC1, and E2F signaling, and deregulated p53 signaling (IP6K2 only) in C4 mCRPC cells. Our study highlights the necessity of performing individual validation of candidate hits from genome-wide CRISPR screens. Further studies are needed to assess the generalizability and translational potential of these findings.
Topics: Male; Humans; Docetaxel; Prostatic Neoplasms, Castration-Resistant; CRISPR-Cas Systems; Early Detection of Cancer; Nitriles; Cell Line; Treatment Outcome; Antineoplastic Combined Chemotherapy Protocols; GTPase-Activating Proteins
PubMed: 37270558
DOI: 10.1038/s41598-023-35950-7 -
JAMA Network Open Nov 2023Patients with high-grade prostate cancer with low levels of prostate-specific antigen (PSA; <4 ng/mL) are at high risk of mortality, necessitating an improved treatment... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Patients with high-grade prostate cancer with low levels of prostate-specific antigen (PSA; <4 ng/mL) are at high risk of mortality, necessitating an improved treatment paradigm.
OBJECTIVE
To assess for these patients whether adding docetaxel to standard of care (SOC) treatment is associated with decreased prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM).
DATA SOURCES
PubMed search from 2000 to 2022.
STUDY SELECTION
Five prospective randomized clinical trials (RCTs) performed in the US, France, and the United Kingdom evaluating SOC treatment with radiotherapy and androgen deprivation therapy (ADT) or with radical prostatectomy vs SOC plus docetaxel.
DATA EXTRACTION AND SYNTHESIS
Individual data were included from patients with nonmetastatic prostate cancer, a PSA level of less than 4 ng/mL, and a Gleason score of 8 to 10. Patients initiated treatment between February 21, 2006, and December 31, 2015 (median follow-up, 7.1 [IQR, 5.4-9.9] years). Data were analyzed on December 16, 2022.
MAIN OUTCOMES AND MEASURES
Hazard ratio (HR) of ACM and subdistribution HR (sHR) of PCSM adjusted for performance status (1 vs 0 or good health), Gleason score (9 or 10 vs 8), tumor category (T3-T4 vs T1-T2 or TX), and duration of ADT (2 years vs 4-6 months).
RESULTS
From a cohort of 2184 patients, 145 patients (6.6%) in 4 RCTs were eligible (median age, 63 [IQR, 46-67] years). Thirty-one patients died, and of these deaths, 22 were due to prostate cancer. Performance status was 0 for 139 patients (95.9%) and 1 for 6 patients (4.1%). A reduced but nonsignificant risk of ACM (HR, 0.51 [95% CI, 0.24-1.09]) and PCSM (sHR, 0.42 [95% CI, 0.17-1.02]) was associated with patients randomized to SOC plus docetaxel compared with SOC. The risk reduction in ACM (HR, 0.46 [95% CI, 0.21-1.02]) was more pronounced among patients with a performance status of 0 and was significant for PCSM (sHR, 0.30 [95% CI, 0.11-0.86]).
CONCLUSIONS AND RELEVANCE
Adding docetaxel to SOC treatment for patients who are in otherwise good health with a PSA level of less than 4 ng/mL and a Gleason score of 8 to 10 was associated with a significant reduction in PCSM and therefore has the potential to improve prognosis.
Topics: Male; Humans; Middle Aged; Docetaxel; Prostate-Specific Antigen; Prostatic Neoplasms; Prostate; Prostatectomy; Randomized Controlled Trials as Topic
PubMed: 37910103
DOI: 10.1001/jamanetworkopen.2023.40787 -
Biomedicine & Pharmacotherapy =... Apr 2023Prostate cancer is among most malignant tumors around the world and this urological tumor can be developed as result of genomic mutations and their accumulation during... (Review)
Review
Prostate cancer is among most malignant tumors around the world and this urological tumor can be developed as result of genomic mutations and their accumulation during progression towards advanced stage. Due to lack of specific symptoms in early stages of prostate cancer, most cancer patients are diagnosed in advanced stages that tumor cells display low response to chemotherapy. Furthermore, genomic mutations in prostate cancer enhance the aggressiveness of tumor cells. Docetaxel and paclitaxel are suggested as well-known compounds for chemotherapy of prostate tumor and they possess a similar function in cancer therapy that is based on inhibiting depolymerization of microtubules, impairing balance of microtubules and subsequent delay in cell cycle progression. The aim of current review is to highlight mechanisms of paclitaxel and docetaxel resistance in prostate cancer. When oncogenic factors such as CD133 display upregulation and PTEN as tumor-suppressor shows decrease in expression, malignancy of prostate tumor cells enhances and they can induce drug resistance. Furthermore, phytochemicals as anti-tumor compounds have been utilized in suppressing chemoresistance in prostate cancer. Naringenin and lovastatin are among the anti-tumor compounds that have been used for impairing progression of prostate tumor and enhancing drug sensitivity. Moreover, nanostructures such as polymeric micelles and nanobubbles have been utilized in delivery of anti-tumor compounds and decreasing risk of chemoresistance development. These subjects are highlighted in current review to provide new insight for reversing drug resistance in prostate cancer.
Topics: Male; Humans; Docetaxel; Paclitaxel; Taxoids; Drug Resistance, Neoplasm; Prostatic Neoplasms; Cell Line, Tumor
PubMed: 36804123
DOI: 10.1016/j.biopha.2023.114392 -
Current Oncology (Toronto, Ont.) Apr 2023The treatment paradigm for metastatic castrate-sensitive prostate cancer (mCSPC) has evolved rapidly in the past decade with the approval of several life-prolonging... (Review)
Review
The treatment paradigm for metastatic castrate-sensitive prostate cancer (mCSPC) has evolved rapidly in the past decade with the approval of several life-prolonging therapies including docetaxel chemotherapy and multiple androgen receptor pathway inhibitors (ARPI) in combination with androgen deprivation therapy (ADT). Recently reported phase-three trials have demonstrated a survival benefit of upfront triplet therapy with ADT, docetaxel plus either abiraterone acetate or darolutamide when compared to ADT plus docetaxel alone. However, multiple questions including the incremental benefit of docetaxel to a combination of ADT and ARPI, the timing of ARPI, optimal patient selection for triplet therapy and clinical and genomic biomarkers still remain to be answered. Moreover, real-world data suggest suboptimal treatment intensification with many patients treated with ADT alone highlighting challenges in implementation. In this article, we review the phase-three data associated with triplet therapy in mCSPC. We also discuss the knowledge gaps that exist despite the completion of these studies and how ongoing studies are likely to change the paradigm in the near future. Finally, we provide a simple algorithm based on current data that clinicians can use in daily practice to select patients for appropriate treatment strategies.
Topics: Male; Humans; Prostatic Neoplasms; Docetaxel; Androgen Antagonists; Standard of Care; Abiraterone Acetate
PubMed: 37185445
DOI: 10.3390/curroncol30040332 -
Molecular Oncology Oct 2023Chemotherapy remains the standard treatment for triple-negative breast cancer (TNBC); however, chemoresistance compromises its efficacy. The RNA-binding protein Hu...
Chemotherapy remains the standard treatment for triple-negative breast cancer (TNBC); however, chemoresistance compromises its efficacy. The RNA-binding protein Hu antigen R (HuR) could be a potential therapeutic target to enhance the chemotherapy efficacy. HuR is known to mainly stabilize its target mRNAs, and/or promote the translation of encoded proteins, which are implicated in multiple cancer hallmarks, including chemoresistance. In this study, a docetaxel-resistant cell subline (231-TR) was established from the human TNBC cell line MDA-MB-231. Both the parental and resistant cell lines exhibited similar sensitivity to the small molecule functional inhibitor of HuR, KH-3. Docetaxel and KH-3 combination therapy synergistically inhibited cell proliferation in TNBC cells and tumor growth in three animal models. KH-3 downregulated the expression levels of HuR targets (e.g., β-Catenin and BCL2) in a time- and dose-dependent manner. Moreover, KH-3 restored docetaxel's effects on activating Caspase-3 and cleaving PARP in 231-TR cells, induced apoptotic cell death, and caused S-phase cell cycle arrest. Together, our findings suggest that HuR is a critical mediator of docetaxel resistance and provide a rationale for combining HuR inhibitors and chemotherapeutic agents to enhance chemotherapy efficacy.
Topics: Animals; Humans; Apoptosis; Cell Line, Tumor; Cell Proliferation; Docetaxel; RNA-Binding Proteins; Triple Negative Breast Neoplasms
PubMed: 37357618
DOI: 10.1002/1878-0261.13478