Home > Treatments > Chemotherapy > Drugs > Paclitaxel


"A cyclodecane isolated from the bark of the Pacific yew tree, TAXUS BREVIFOLIA. It stabilizes MICROTUBULES in their polymerized form leading to cell death." (MeSH 2013)

Found this page useful?

Web Resources: Paclitaxel
Latest Research Publications

Web Resources: Paclitaxel (6 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Nishimura M, Onoe T, Sakai H, et al.
Safety and Relative Dose Intensity of Dose-dense Doxorubicin and Cyclophosphamide Followed by Dose-dense Paclitaxel.
Anticancer Res. 2019; 39(8):4379-4383 [PubMed] Related Publications
BACKGROUND/AIM: Dose-dense doxorubicin and cyclophosphamide (ddAC) followed by dose-dense paclitaxel (ddP) (ddAC-P) has improved disease-free survival of patients with breast cancer. The aim of this study was to evaluate the safety and relative dose intensity (RDI) of ddAC-P administered together with pegfilgrastim.
PATIENTS AND METHODS: Between May 2015 and Aug 2017, 44 patients were retrospectively reviewed; they were administered 4 cycles of ddAC, followed by 4 cycles of ddP. Pegfilgrastim (3.6 mg) was administered in every cycle.
RESULTS: The mean RDIs for ddAC-P, ddAC, and ddP were 95.0%, 94.5%, and 93.3%, respectively. The prevalence of high RDIs (≥85%) for ddAC-P, ddAC, and ddP was 90.9%, 84.1%, and 88.6%, respectively. Seven of the 10 patients with low RDIs experienced grade 1 or 2 fever.
CONCLUSION: DdAC-P administered together with pegfilgrastim (3.6 mg) appears to be feasible and maintains RDI in most of Japanese patients with breast cancer. Rapid evaluation and proper management of fever may prevent low RDI.

Lin L, Zheng Y, Wu Z, et al.
A tumor microenvironment model coupled with a mass spectrometry system to probe the metabolism of drug-loaded nanoparticles.
Chem Commun (Camb). 2019; 55(69):10218-10221 [PubMed] Related Publications
This study describes a novel integrated microfluidic platform with microvessel network channels which are connected to an electrospray ionization-mass spectrometer (ESI-MS), allowing real-time probing of nanoparticle (NP) drug delivery in vascular niche around tumors and understanding the drug delivery efficacy in a realistic tumor microenvironment.

Liu M, Gong C, Xu R, et al.
MicroRNA-5195-3p enhances the chemosensitivity of triple-negative breast cancer to paclitaxel by downregulating EIF4A2.
Cell Mol Biol Lett. 2019; 24:47 [PubMed] Free Access to Full Article Related Publications
Background: Chemotherapy based on paclitaxel (PTX) is the standard treatment for a range of cancers, including triple-negative breast cancer (TNBC), but the increasing development of resistance has reduced/has negatively impacted its clinical utility. A previous study demonstrated that miR-5195-3p could suppress lung cancer cell growth. This study was designed to investigate whether miR-5195-3p attenuates chemoresistance to PTX by regulating target genes in TNBC cells.
Methods: The study used both PTX-resistant tumor tissues and PTX-resistant TNBC cell lines. The expression of miR-5195-3p was determined using quantitative real-time PCR. Cell viability, cell cycle distribution and apoptosis were analyzed using CCK-8 and flow cytometry assays. The target genes of miR-5195-3p were predicted with bioinformatics analysis and confirmed using the luciferase reporter assay.
Results: MiR-5195-3p expression was lower in PTX-resistant tumor tissues and PTX-resistant TNBC cell lines. Upregulation of miR-5195-3p enhanced the sensitivity of PTX-resistant TNBC cells to PTX treatment. EIF4A2 was confirmed as a potential target of miR-5195-3p. EIF4A2 knockdown imitated the effects of miR-5195-3p on chemosensitivity, while restoration of EIF4A2 rescued them.
Conclusion: These data demonstrate that miR-5195-3p might be a potential therapeutic target to reverse chemoresistance in TNBC through its targeting of EIF4A2.

Xie F, De Clercq K, Vervaet C, et al.
Model-based analysis of treatment effects of paclitaxel microspheres in a microscopic peritoneal carcinomatosis model in mice.
Pharm Res. 2019; 36(9):127 [PubMed] Related Publications
PURPOSE: Paclitaxel (PTX)-loaded genipin-crosslinked gelatin microspheres (GP-MS) are a prolonged IP delivery system under development for the treatment of peritoneal minimal residual disease (pMRD). Here, we show the use of a pharmacokinetic-pharmacodynamic (PKPD) modelling approach to inform the formulation development of PTX-GP-MS in a mice pMRD model.
METHODS: PTX blood concentrations and survival data were obtained in Balb/c Nu mice receiving different single IP doses (7.5 and/or 35 mg/kg) of PTX-ethanolic loaded GP-MS (PTX
RESULTS: A PKPD model was developed that simultaneously describes the competing effects of treatment efficacy (driven by peritoneal concentration) and toxicity (driven by blood concentration) of PTX on survival. Clear survival advantages of PTX
CONCLUSIONS: The model predicts that the dose range of 7.5-15 mg/kg of PTX

Zhu L, Chen L
Progress in research on paclitaxel and tumor immunotherapy.
Cell Mol Biol Lett. 2019; 24:40 [PubMed] Free Access to Full Article Related Publications
Paclitaxel is a well-known anticancer agent with a unique mechanism of action. It is considered to be one of the most successful natural anticancer drugs available. This study summarizes the recent advances in our understanding of the sources, the anticancer mechanism, and the biosynthetic pathway of paclitaxel. With the advancement of biotechnology, improvements in endophytic fungal strains, and the use of recombination techniques and microbial fermentation engineering, the yield of extracted paclitaxel has increased significantly. Recently, paclitaxel has been found to play a large role in tumor immunity, and it has a great potential for use in many cancer treatments.

Tao L, Wu YQ, Zhang SP
MiR-21-5p enhances the progression and paclitaxel resistance in drug-resistant breast cancer cell lines by targeting PDCD4.
Neoplasma. 2019; 2019 [PubMed] Related Publications
MiR-21-5p has been identified as an oncogene to enhance human tumor progression. Here, we explored the mechanism by which miR-21-5p regulated the progression and paclitaxel (PTX) resistance in drug-resistant breast cancer (BC) cell lines. qRT-PCR assays were used to assess the expression levels of miR-21-5p and PDCD4 mRNA, and western blotting was used to detect PDCD4 protein level in PTX-resistant BC cell lines. Dual-luciferase reporter assay was used to observe the interaction between miR-21-5p and PDCD4 in PTX-resistant BC cell lines. Cell proliferation ability and IC50 values of PTX were measured by CCK-8 assay, cell cycle progression and apoptosis were determined with flow cytometry analysis, and cell migration and invasion capacities were analyzed using Transwell assay. Xenograft mice assay was used to validate the important role of miR-21-5p as a regulator on PTX-resistance BC cells growth in vivo. Then, we found that miR-21-5p was upregulated and PDCD4 was downregulated in BC tissues and PTX-resistant BC cell lines. MiR-21-5p silencing or PDCD4 overexpression ameliorated PTX resistance and inhibited the progression in PTX-resistant BC cell lines. Moreover, PDCD4 was demonstrated to be a direct target of miR-21-5p. MiR-21-5p exerted its regulatory effect by PDCD4 in PTX-resistant BC cell lines. Additionally, miR-21-5p silencing inhibited tumor growth in vivo. Therefore, our study demonstrated that miR-21-5p silencing ameliorated PTX resistance and inhibited the progression in PTX-resistant BC cell lines at least partly by targeting PDCD4, providing miR-21-5p as an effective therapeutic target for PTX-resistant BC treatment.

Mu X, Chen M, Xiao B, et al.
EZH2 Confers Sensitivity of Breast Cancer Cells to Taxol by Attenuating p21 Expression Epigenetically.
DNA Cell Biol. 2019; 38(7):651-659 [PubMed] Related Publications
Breast cancer is the leading cause of death in women. Although numerous clinical regimens are used to treat breast cancer and manifest satisfied efficacy, drug resistance is emerging as the major obstacle to their long-term use. It is critically necessary to decipher the molecular mechanism underlying this process to obtain improved and long-term use of each regimen. In the present study, we showed the negative relationship between EZH2 and chemoresistance to taxol in breast cancer cells. EZH2 interference was capable of decreasing while overexpression increasing apoptosis of breast cancer cells challenged with taxol. Meanwhile, p21, the inhibitor of cell cycle entry, interference upregulated, while overexpression downregulated apoptosis induced by taxol. Mechanistically, EZH2 was recruited to the promoter of p21 accompanied with H3K27me3 enrichment and transcription silencing. Collectively, EZH2 attenuates chemoresistance of breast cancer cells to taxol by dampening p21 epigenetically.

Zhang H, Zhao B, Wang X, et al.
LINC00511 knockdown enhances paclitaxel cytotoxicity in breast cancer via regulating miR-29c/CDK6 axis.
Life Sci. 2019; 228:135-144 [PubMed] Related Publications
AIMS: Drug resistance is becoming a major clinical challenge to the success of breast cancer treatment. Compelling evidence has shown the association between the deregulated long non-coding RNAs (lncRNAs) and drug resistance in various malignancies. However, the effects of long intergenic noncoding RNA 00511 (LINC00511), a newly identified oncogenic lncRNA, on the drug resistance of breast cancer cells remain unknown.
MAIN METHODS: RT-qPCR was performed to detect the expressions of LINC00511, miR-29c, and cyclin dependent kinase 6 (CDK6) in breast cancer tissues and cells. Pearson correlation analysis was used to analyze the correlation between miR-29c, CDK6 and LINC00511 expression in breast cancer tissues. The interactions between LINC00511, CDK6 and miR-29c were explored by luciferase reporter assay, RT-qPCR and western blot. MTT assay and flow cytometry analysis were applied to evaluate paclitaxel cytotoxicity.
KEY FINDINGS: LINC00511 and CDK6 were upregulated while miR-29c was downregulated in breast cancer tissues and cells. miR-29c was negatively correlated with LINC00511 and CDK6 expression while LINC00511 was positively correlated with CDK6 expression in breast cancer tissues. LINC0051 directly interacted with miR-29c to suppress its expression. LINC00511 knockdown enhanced paclitaxel cytotoxicity in breast cancer cells by upregulating miR-29c. CDK6 was identified as a target of miR-29c. CDK6 knockdown attenuated the effects of miR-29c inhibition on paclitaxel cytotoxicity in breast cancer cells. LINC00511 positively regulated CDK6 expression in breast cancer cells.
SIGNIFICANCE: LINC00511 knockdown enhanced paclitaxel cytotoxicity in breast cancer cells via regulating miR-29c/CDK6 axis.

Xie Z, Wei Y, Xu J, et al.
Alkaloids from Piper nigrum Synergistically Enhanced the Effect of Paclitaxel against Paclitaxel-Resistant Cervical Cancer Cells through the Downregulation of Mcl-1.
J Agric Food Chem. 2019; 67(18):5159-5168 [PubMed] Related Publications
In the current study, nine amide alkaloids, including two new dimeric amides and a new natural product, were identified from Piper nigrum. Among them, seven compounds sensitized paclitaxel-resistant cervical cancer cells HeLa/PTX to paclitaxel. Piperine was a major component obtained from Piper nigrum, and its sensitization mechanism was investigated. Combination treatment enhanced cell apoptosis, which was mediated by downregulation of phospho-Akt and Mcl-1. Piperine (50 μM) combined with paclitaxel (200 nM) downregulated Mcl-1 protein expression with a decrease of 35.9 ± 9.5% ( P < 0.05). Moreover, overexpression of Mcl-1 attenuated the inhibitory effect of this combination. Furthermore, combination treatments of six dimeric amide alkaloids and paclitaxel all downregulated Mcl-1 protein expression with a decrease ranging from 23.5 ± 9.7% to 41.7 ± 7.2% ( P < 0.05). We reveal, for the first time, that dimeric amide alkaloids from plants possess a remarkable sensitization effect on cancer cells to paclitaxel.

Hayase S, Yamada L, Ujiie D, et al.
Clinical usefulness of ramucirumab plus paclitaxel for unresectable and recurrent gastric cancer.
Fukushima J Med Sci. 2019; 65(1):6-12 [PubMed] Free Access to Full Article Related Publications
Introduction Recently in Japan, Ramucirumab (RAM) became the first anti-angiogenic agent to be approved for second-line treatment of gastric cancer. In the present study, we aimed to evaluate the efficacy and safety of RAM plus paclitaxel (PTX) in patients with unresectable and recurrent gastric cancer in our institution.Patients and Methods The subjects were 11 patients with unresectable and recurrent gastric cancer who received RAM plus PTX as a second- or later-line treatment at our hospital between June 2015 and September 2017, after the failure of previously-attempted treatments. We assessed the efficacy and safety of RAM plus PTX, and also compared them between patients aged <75 years (n=6) and those aged ≥75 (n=5), by performing a retrospective analysis based on the data obtained from daily clinical practice for gastric cancer treatment.Results Objective tumor response was observed in one of the 11 patients (9.1%) with partial response, and disease control was seen in the remaining 10 (90.9%). The median overall survival (OS) and progression-free survival (PFS) of the patients were 20.8 months (95% CI 7.8-NA (not applicable)) and 11.3 months (95% CI 6.5-NA), respectively. There were no serious adverse events. The median OS for the <75 years group and ≥75 years group was NA (due to short follow-up period) and 20.8 months (p = 0.336), respectively, and their respective median PFS rates were 9.4 and 11.3 months (p = 0.492). The difference of rate of adverse events was not significant between the two age groups in the present study, though the number of adverse events was not sufficient.Conclusion The results of the present study suggest that the combination chemotherapy of RAM and PTX was effective in unresectable and recurrent gastric cancer patients as a second- or later-line therapy, and has been shown to be safe and feasible in elderly patients.

Öztürk Y, Günaydın C, Yalçın F, et al.
Resveratrol Enhances Apoptotic and Oxidant Effects of Paclitaxel through TRPM2 Channel Activation in DBTRG Glioblastoma Cells.
Oxid Med Cell Longev. 2019; 2019:4619865 [PubMed] Free Access to Full Article Related Publications
Numerous studies have reported a strong association between increased production of reactive oxygen species (ROS) and the pathobiology of several diseases, and cancer in particular. Therefore, manipulation of cellular oxidative stress levels represents an important therapeutic target. Recently, resveratrol (RESV), a naturally occurring phytochemical, has been shown to sensitize several cell lines to the anticancer effects of other chemotherapeutic agents, including paclitaxel (PAX). However, the molecular mechanisms of action of RESV through oxidative sensitive TRPM2 channel activation remain unclear. The aim of this study was to evaluate the effect of combination therapy of RESV and PAX on activation of TRPM2 in DBTRG glioblastoma cells. DBTRG cells were divided into four treatment groups: control, RESV (50 

Hwang ST, Kim C, Lee JH, et al.
Cycloastragenol can negate constitutive STAT3 activation and promote paclitaxel-induced apoptosis in human gastric cancer cells.
Phytomedicine. 2019; 59:152907 [PubMed] Related Publications
BACKGROUND: Cycloastragenol (CAG), a triterpene aglycone is commonly prescribed for treating hypertension, cardiovascular disease, diabetic nephropathy, viral hepatitis, and various inflammatory-linked diseases.
HYPOTHESIS: We investigated CAG for its action on signal transducer and activator of transcription 3 (STAT3) activation cascades, and its potential to sensitize gastric cancer cells to paclitaxel-induced apoptosis.
METHODS: The effect of CAG on STAT3 phosphorylation and other hallmarks of cancer was deciphered using diverse assays in both SNU-1 and SNU-16 cells.
RESULTS: We observed that CAG exhibited cytotoxic activity against SNU-1 and SNU-16 cells to a greater extent as compared to normal GES-1 cells. CAG predominantly caused negative regulation of STAT3 phosphorylation at tyrosine 705 through the abrogation of Src and Janus-activated kinases (JAK1/2) activation. We noted that CAG impaired translocation of STAT3 protein as well as its DNA binding activity. It further decreased cellular proliferation and mediated its anticancer effects predominantly by causing substantial apoptosis rather than autophagy. In addition, CAG potentiated paclitaxel-induced anti-oncogenic effects in gastric tumor cells.
CONCLUSIONS: Our results indicate that CAG can function to impede STAT3 activation in human gastric tumor cells and therefore it may be a suitable candidate agent for therapy of gastric cancer.

Ali Hassan A, Ibrahim NY, Jassen MAR
Concurrent Paclitaxel and Radiotherapy for Node Positive Breast Cancer.
Gulf J Oncolog. 2019; 1(29):14-21 [PubMed] Related Publications
BACKGROUND: Concurrent chemo-radiotherapy in breast cancer (BC) may yield better local control with minimal toxicity in node positive patients. The feasibility of paclitaxel with radiotherapy was assessed for tolerability, cosmetic outcome as well as local control.
METHODS: A prospective feasibility study on forty-three female breast cancer with stage II-III was conducted after definite surgery (modified radical mastectomy and breast conservative surgery). Adjuvant chemotherapy given was 4 cycles AC (Doxorubicin 60mg/m2+ cyclophosphamide 600mg/m2) followed by 4 cycles of Paclitaxel 60mg/m2 weekly for 12 weeks concurrent with 3D Conformal radiotherapy in a dose of 5Gy/20ttt/4wks to the whole breast and supraclavicular nodal region. Boost of 10Gy/5ttt was given to the tumor bed in conservative cases. Evaluation of lung function was done by carbon monoxide diffusion. Radiotherapy toxicity and breast cosmesis were assessed by the RTOG and Harvard criteria respectively. The cosmesis was assessed and scored at the beginning and end of RT and every 6 months thereafter. This was done by patient (subjective score) and physician (objective score) by comparing it with the contralateral untreated breast.
RESULTS: After a median follow up of 36 months, the overall survival and disease-free survival were 95% and 92.5% respectively with no local relapse or radiation pneumonitis. There was no significant change in carbon monoxide diffusion after radiotherapy (p: 0.55). There was 15% delay in radiotherapy mainly due to acute GIII skin toxicity (10%), followed equally by mucositis and wound gap (2.5%). The volume of the irradiated breast was correlated with acute cosmetic effect (p = 0.057) but not on the late skin toxicity (p = 0.56). At the last follow up, the majority of patients declared excellent score in 62.5%, good in 20%, fair in 10% and poor in 7.5%. Subjective patient's satisfaction for the shape, color and size of the treated breast was 93%.
CONCLUSION: Concurrent chemo-radiotherapy with weekly paclitaxel minimized the treatment duration with acceptable tolerance, cosmesis and good local control.

Tokunaga S, Takashima T, Kashiwagi S, et al.
Neoadjuvant Chemotherapy With Nab-paclitaxel Plus Trastuzumab Followed by 5-Fluorouracil/Epirubicin/Cyclophosphamide for HER2-positive Operable Breast Cancer: A Multicenter Phase II Trial.
Anticancer Res. 2019; 39(4):2053-2059 [PubMed] Related Publications
AIM: This study was conducted in order to evaluate the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus trastuzumab followed by 5-fluorouracil/ epirubicin/cyclophosphamide (FEC) in a neoadjuvant chemotherapy (NAC) setting for patients with human epidermal growth factor receptor 2 (HER2)-positive operable breast cancer.
PATIENTS AND METHODS: Each patient received four cycles of 260 mg/m
RESULTS: Twenty-nine patients were analyzed for the efficacy and safety of this treatment. All patients completed four cycles of nab-paclitaxel and trastuzumab, and 28 patients completed four cycles of FEC. Twenty-seven patients subsequently underwent surgery. The pCR rate was 74.0%. The most frequent toxicity was sensory neuropathy (96.6%), but grade 3 neuropathy rate was 3.4%.
CONCLUSION: Nab-paclitaxel plus trastuzumab followed by FEC in patients with HER2-positive operable breast cancer is considerably effective and well tolerated.

Jeleniewicz W, Cybulski M, Nowakowski A, et al.
Anticancer Res. 2019; 39(4):1821-1827 [PubMed] Related Publications
BACKGROUND/AIM: Ovarian cancer is the most frequent cause of death in women among gynecological cancers in Poland. MMP-2 and MMP-9 are frequently dysregulated in cancers and they are considered as potential biomarkers. Our goal was to assess the associations between MMP-2 and MMP-9 mRNA expression, clinicopathological parameters and patients' response to chemotherapy.
MATERIALS AND METHODS: We evaluated MMP-2 and MMP-9 mRNA expression in epithelial ovarian cancer (EOC) tissues from 44 untreated patients, four ovarian cancer cell lines, and human skin fibroblasts (HSF). The expression of both MMPs was estimated using qPCR.
RESULTS: MMP-2 expression was significantly higher (p=0.020) in EOCs sensitive to chemotherapy compared to resistant and refractory tumors. The highest MMP-2 expression was found in HSF and MMP-9 expression was the highest in EOCs (p<0.001). The expression of neither MMP was significantly associated with patients' overall survival (OS).
CONCLUSION: MMP-2 may be engaged in early stages of ovarian carcinogenesis. MMP-2 expression in EOCs may discriminate patients with a favorable response to first line chemotherapy.

Mery B, Rowinski E, Vallard A, et al.
Advocacy for a New Oncology Research Paradigm: The Model of Bevacizumab in Triple-Negative Breast Cancer in a French Cohort Study.
Oncology. 2019; 97(1):1-6 [PubMed] Related Publications
BACKGROUND: Triple-negative breast cancer remains a disease with poor prognosis and few treatment options, due to the lack of therapeutic targets. Bevacizumab, the first anti-VEGF agent approved in the treatment of cancer, has demonstrated efficacy in breast cancer in combination with paclitaxel for the first-line treatment of HER2-negative metastatic breast cancer. Despite the fact that the benefit was particularly significant for triple-negative breast cancer with its approval in 2008 by the FDA, this decision was later reversed as there was no improvement in overall survival in addition to significant costs.
OBJECTIVES: The scope of the present study is to focus on the role of bevacizumab in triple-negative breast cancer through the analysis of overall survival, progression-free survival, and cost benefit among 45 patients in a French monocentric study and to discuss new paradigms of endpoints.
METHODS: All patients diagnosed with metastatic triple-negative breast cancer, for whom first-line treatment was bevacizumab in combination with paclitaxel between January 2011 and April 2018 were included in this single-center retrospective study, and a chart review of all recruited subjects was performed from medical records.
RESULTS: In this real-life study among 45 patients with metastatic triple-negative breast cancer, bevacizumab provided a significant benefit for a category of patients, with longer median progression-free survival and the ability of maintenance therapy associated to limited side effects.
CONCLUSIONS: Beyond being the phoenix of breast oncology and a magnet of controversy, the case of bevacizumab in metastatic breast cancer highlights one of the greatest challenges in oncology, namely to balance modest clinical benefits with exponential costs. A balance needs to be found between health care affordability, high price of progress, and the best medical decision for the patients, in order to avoid the "unbreathable tipping point" we are actually dealing with.

Mendes LP, Sarisozen C, Luther E, et al.
Surface-engineered polyethyleneimine-modified liposomes as novel carrier of siRNA and chemotherapeutics for combination treatment of drug-resistant cancers.
Drug Deliv. 2019; 26(1):443-458 [PubMed] Free Access to Full Article Related Publications
Modification of nanoparticle surfaces with PEG has been widely considered the gold standard for many years. However, PEGylation presents controversial and serious challenges including lack of functionality, hindered cellular interaction, allergic reactions, and stimulation of IgM production after repetitive dosing that accelerates blood clearance of the nanoparticles. We report the development of novel liposomal formulations surface-modified with a low molecular weight, branched polyethyleneimine (bPEI)-lipid conjugate for use as an alternative to PEG. The formulations had very good stability characteristics in ion- and protein-rich mediums. Protein adsorption onto the liposomal surface did not interfere with the cellular interaction. bPEI-modified liposomes (PEIPOS) showed enhanced association with three different cell lines by up to 75 times compared to plain or PEGylated liposomes and were without carrier toxicity. They also penetrated the deeper layers of 3D spheroids. Encapsulating paclitaxel (PTX) into PEIPOS did not change its main mechanism of action. PEIPOS complexed and intracellularly delivered siRNAs and downregulated resistance-associated proteins. Finally, tumor growth inhibition was observed in a mouse ovarian xenograft tumor model, without signs of toxicity, in animals treated with the siRNA/PTX co-loaded formulation. These complex-in-nature but simple-in-design novel liposomal formulations constitute viable and promising alternatives with added functionality to their PEGylated counterparts.

Li J, Chen Q, Deng Z, et al.
KRT17 confers paclitaxel-induced resistance and migration to cervical cancer cells.
Life Sci. 2019; 224:255-262 [PubMed] Related Publications
AIM: To understand potential pro-oncological effects of lower dose paclitaxel treatment in cervical cancer cells, we investigated the potential roles of KRT17 on migration and proliferation of cervical cancer cells which might respond to cytoskeletal-based drugs treatments.
MATERIALS AND METHODS: We extracted the clinic data of cervical cancer patients from TCGA database to investigate mRNA expression of different keratins. HPV genotypes were identified by reverse transcription PCR. krt17 mRNA and EMT markers were quantified by real-time PCR. krt17 and EMT markers protein were immunoblotted by western blot. Cell viability was detected by CCK8. Cell migration was performed by transwell migration assay.
KEY FINDINGS: Our results showed that HPV16 infection correlated with the expression of KRT17 in cervical cancer cell lines. KRT17 knockdown would decrease Snail2 and elevate E-Cadherin to inhibit migration of Caski cells and SiHa cells. Lower dose of paclitaxel promoted SiHa proliferation, it also significantly promoted the migration of Caski cells. Otherwise, colchicine and higher dose of paclitaxel dose-dependently suppressed the proliferation and migration of Caski cells and SiHa cells. Moreover, KRT17 knockdown significantly facilitated cytoskeletal-based drugs to inhibit migration and induce cytotoxicity in cervical cancer cells.
SIGNIFICANCE: KRT17 played pivotal oncogenic roles in cell survival, migration and paclitaxel-induced resistance of cervical cancer cells. Thus, KRT17 would serve as a promising target for compromising paclitaxel-induced resistance and metastasis.

Di Bartolomeo M, Niger M, Morano F, et al.
Assessment of Ramucirumab plus paclitaxel as switch maintenance versus continuation of first-line chemotherapy in patients with advanced HER-2 negative gastric or gastroesophageal junction cancers: the ARMANI phase III trial.
BMC Cancer. 2019; 19(1):283 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Platinum/fluoropyrimidine regimens are the backbone of first-line chemotherapy for advanced gastric cancer (AGC). However response rates to first line chemotherapy range from 30 to 50% and disease progression occurs after 4-6 cycles. The optimal duration of first-line therapy is still unknown and its continuation until disease progression represents the standard. However this strategy is often associated with cumulative toxicity and rapid development of drug resistance. Moreover, only about 40% of AGC pts. are eligible for second-line treatment.
METHODS: This is a randomized, open-label, multicenter phase III trial. It aims at assessing whether switch maintenance to ramucirumab plus paclitaxel will extend the progression-free survival (PFS) of subjects with HER-2 negative AGC who have not progressed after 3 months of a first-line with a platinum/fluoropyrimidine regimen (either FOLFOX4, mFOLFOX6 or XELOX). The primary endpoint is to compare Progression-Free Survival (PFS) of patients in ARM A (switch maintenance to ramucirumab and placlitaxel) versus ARM B (continuation of the same first-line therapy with oxaliplatin/fluoropyrimidine). Secondary endpoints are: overall survival, time-to-treatment failure, overall response rate, duration of response, percentage of patients that will receive a second line therapy according to arm treatment, safety, quality of life. Exploratory studies including Next-Generation Sequencing (NGS) in archival tumor tissues are planned in order to identify potential biomarkers of primary resistance and prognosis.
DISCUSSION: The ARMANI study estimates if patients treated with early swich with ramucirumab plus paclitaxel received benefit when compared to those treated with continuation of first line therapy. The hypothesis is that the early administration of an active, non-cross resistant second-line regimen such as ramucirumab plus paclitaxel may prolong the time in which patients are progression-free, and consequently have a better quality of life. Moreover, this strategy may rescue all those subjects that become ineligible for second-line therapy due to the rapid deterioration of health status after the first disease progression.
TRIAL REGISTRATION: ARMANI is registered at ClinicalTrials.gov ( NCT02934464 , October 17, 2016) and EudraCT(2016-001783-12, April 202,016).

Rogers JE, Xiao L, Amlashi FG, et al.
Ramucirumab and Paclitaxel Administered Every 2 Weeks (mRAINBOW Regimen) in Advanced Gastroesophageal Adenocarcinoma.
Oncology. 2019; 96(5):252-258 [PubMed] Related Publications
BACKGROUND: The RAINBOW trial established ramucirumab combined with paclitaxel as a second-line option in metastatic gastric and gastroesophageal junction (GEJ) adenocarcinoma. Ramucirumab was given on days 1 and 15 with paclitaxel on days 1, 8, and 15 of a 28-day cycle. The median overall survival (OS) was significantly longer with ramuciru-mab plus paclitaxel (p = 0.017), and it led to 41% grade 3 or higher neutropenia. We review our experience with both ramucirumab plus paclitaxel given biweekly (mRAINBOW) to assess efficacy and safety.
OBJECTIVES: The primary objective was to assess OS. Secondary end points were progression-free survival (PFS), overall response, and safety.
METHODS: We identified 129 patients retrospectively from our database between November 2014 and May 2017. Patients were included if they were followed up at our institution.
RESULTS: Median doses given were ramucirumab 8 mg/kg i.v. plus paclitaxel 110 mg/m2 i.v. given once every 2 weeks. The median performance status was 1, and ∼60% had poorly differentiated histology; 55.8% had progression in < 6 months on first-line therapy, and the majority had measurable cancer. Median overall OS and PFS for the entire cohort was 9.4 months (95% CI: 8.05-10.74) and 3.68 months (95% CI: 2.73-4.5), respectively. Median OS was 9.46 months (95% CI: 8.05-14.95) and median PFS was 4.14 months (95% CI: 2.96-5.29) in those patients that received ramucirumab plus paclitaxel in the second-line setting.
CONCLUSION: Biweekly administration of ramucirumab plus paclitaxel did not compromise efficacy. Delays, adjustments, or doses held were similar to the RAINBOW trial, with 31% requiring a dose or schedule modification.

Han S, Dwivedi P, Mangrio FA, et al.
Sustained release paclitaxel-loaded core-shell-structured solid lipid microparticles for intraperitoneal chemotherapy of ovarian cancer.
Artif Cells Nanomed Biotechnol. 2019; 47(1):957-967 [PubMed] Related Publications
The current clinical paradigm for ovarian cancer treatment has a poor prognosis, partially due to the efficacy and toxicity concerns associated with the available chemotherapeutic formulations. To overcome these limitations, we have designed core-shell-structured paclitaxel (PTX) laden solid lipid microparticles (PTX-SLMPs) for intraperitoneal treatment of ovarian cancer. A single-step coaxial electro hydrodynamic atomization (CEHDA) process has been explored to synthesize core-shell structure of PTX-SLMPs with the particle size of 1.76 ± 0.37 µm. Core-shell PTX-SLMPs have high encapsulation efficiency of 94.73% with sustained drug release profile. In vitro evaluation of PTX-SLMPs in SKOV-3 ovarian cancer cells yield significant enhancement in cytotoxicity when compared with Taxol®. In vivo pharmacokinetic study demonstrated slower absorption of PTX into the systemic circulation after intraperitoneal (i.p.) administration of PTX-SLMPs in Wistar rats implying the PTX-SLMPs remained in the peritoneal cavity and released the PTX for prolonged period of time. Through these studies, we have demonstrated the technical potential of core-shell structured PTX-SLMPs, which can enhance passive targeting of PTX to the tumor in the treatment of not only ovarian cancer but also in other peritoneal cancer.

Soltani-Sedeh H, Irani S, Mirfakhraie R, Soleimani M
Potential using of microRNA-34A in combination with paclitaxel in colorectal cancer cells.
J Cancer Res Ther. 2019 Jan-Mar; 15(1):32-37 [PubMed] Related Publications
Background: MicroRNAs are small noncoding RNAs which modulate gene expression at different levels. It has been shown that downregulation of miR-34a occurs in varieties of cancers including colorectal cancer (CRC). In this study, we investigated the potential tumor inhibitory effects of miR-34a alone or in combination with paclitaxel in CRC cells.
Materials and Methods: SW480 cells were transduced with lentiviral overexpressed miR-34a. First, using 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay, the effect of miR-34a induction alone or in combination with paclitaxel on the cell viability and cell proliferation were estimated. Then, the expression level of target genes was measured using quantitative reverse transcription-polymerase chain reaction analysis. Eventually, the role of miR-34a and paclitaxel on cell cycle were determined with flow cytometry.
Results: Gene expression analysis showed that miR-34a downregulates the expression of BCL2 and SIRT1 genes at mRNA level. Furthermore, miR-34a has a potential to reduce cell viability and cell cycle arrest at G1 phase. Combination of paclitaxel with overexpression of miR-34a significantly decreased cell viability compared to cell treated with miR-34a or paclitaxel alone. Interestingly, a combination of miR-34a and paclitaxel arrested cell cycle at two phases.
Conclusion: Our results suggested that combination therapy of miR-34a and paclitaxel could be considered as the potential treatment of CRC.

Zhou J, Sun M, Jin S, et al.
Combined using of paclitaxel and salinomycin active targeting nanostructured lipid carriers against non-small cell lung cancer and cancer stem cells.
Drug Deliv. 2019; 26(1):281-289 [PubMed] Free Access to Full Article Related Publications
The existing of avidity cancer stem cells (CSCs) made it an optical strategy to kill cancer cells and CSCs at the same time. Here, we constructed a CSCs specific nanocarrier naming T-S-NLC using the CD133+ targeting peptide TISWPPR (TR) as the targeting moiety attached to the distal end of PEG on salinomycin (Sal) loaded nanostructured lipid carriers (NLC), its pharmaceutical characteristics proved it 128.73 ± 2.09 nm, anionic spheroid with sustained release profile. It's in vitro targeting effect in CD133+ CSCs indicated that it exhibited superior CSCs internalization over non-modified NLC or free drug. Afterwards, it was used in combination with previously designed EGFR specific A-P-NLC (AEYLR peptide-PEG-modified paclitaxel loaded NLC) to achieve the goal to kill the cancer cells and CSCs, simultaneously. The in vitro tumor targeting effect of T-S-NLC + A-P-NLC was affirmed by cellular uptake and proliferation inhibition effect in NCI-H1299 and S180 cell lines showing advanced results over single preparation groups. In vivo tumor targeting effect in S180 tumor-bearing mice also validated the better tumor accumulative effect of the combined group. Last but not least, the in vivo antitumor effect strongly identified the greater tumor suppression effect of T-S-NLC + A-P-NLC than single preparation groups or combined use of free drugs while maintaining a good living state of the mice. To sum up, the combined usage of PTX and Sal active targeting NLC naming A-P-NLC + T-S-NLC which killed cancer cells and CSCs at the same time was a promising drug delivery system.

Wang D, Huang H, Zhou M, et al.
A thermoresponsive nanocarrier for mitochondria-targeted drug delivery.
Chem Commun (Camb). 2019; 55(28):4051-4054 [PubMed] Related Publications
Mitochondria emerge as an important target for cancer therapy. Herein, by taking advantage of the recently reported high temperature of mitochondria, a well-tuned thermoresponsive nanocarrier was developed for specifically delivering the anticancer drug, paclitaxel (PTX), to mitochondria in cancer cells. The temperature-dependent delivery of drugs to mitochondria represents a novel anticancer strategy.

Hsu FS, Wu JT, Lin JY, et al.
Histone Deacetylase Inhibitor, Trichostatin A, Synergistically Enhances Paclitaxel-Induced Cytotoxicity in Urothelial Carcinoma Cells by Suppressing the ERK Pathway.
Int J Mol Sci. 2019; 20(5) [PubMed] Free Access to Full Article Related Publications
Trichostatin A (TSA), an antifungal antibiotic derived from

Zhao X, Fan J, Wu P, et al.
Chronic chemotherapy with paclitaxel nanoparticles induced apoptosis in lung cancer in vitro and in vivo.
Int J Nanomedicine. 2019; 14:1299-1309 [PubMed] Free Access to Full Article Related Publications
Aim: Paclitaxel (PTX) is an effective antitumor drug. Previous research demonstrated that paclitaxel nanoparticles (PTX-NPs) exhibited the greatest antitumor effect at 15 hours after light onset (15 HALO), but the mechanism in chronic chemotherapy is still unknown. In our study, we investigated whether PTX-NPs regulated Period2 (Per2) during chronic chemotherapy to induce apoptosis in vivo and in vitro.
Methods: To improve the antitumor effect and reduce organ damage induced by PTX treatment, PTX-NPs were prepared using a film dispersion method. Then, A549 cells were treated with PTX-NPs at 0, 5, 10, 15, and 20 HALO. An annexin/PI V-FITC apoptosis kit was measured for apoptosis, and PI was analyzed for cell cycle. The relative mechanism was detected by RT-PCR and Western blotting. Tumor volume and weight were measured to evaluate the antitumor effect of the PTX-NPs, and H&E staining was performed to assess organ damage.
Results: Cell cycle analysis demonstrated that PTX-NPs blocked cell cycle in G2 phase and that the ratio of cell death was significantly increased in A549 cells, while the ratios of cells in G2 phase and of apoptotic cells were highest at 15 HALO. Evaluation of in vivo antitumor activity revealed that PTX-NPs inhibited tumor growth and decreased tumor weight at 15 HALO. RT-PCR and Western blotting demonstrated that PTX-NPs upregulated Per2 mRNA and protein expression, and the highest Per2 expression was observed at 15 HALO in vivo and in vitro. Meanwhile, Bax mRNA and protein expression was upregulated, while Bcl-2 mRNA and protein expression was downregulated after PTX-NPs treatment in vivo. Moreover, H&E staining revealed that PTX-NPs reduced liver damage at 15 HALO.
Conclusion: PTX-NPs exhibited the most effective antitumor activity and reduced liver damage at 15 HALO through upregulation of Per2 expression to induce apoptosis in vivo and in vitro.

Albrecht T, Schnorr B, Kutschera M, Waliszewski MW
Two-Year Mortality After Angioplasty of the Femoro-Popliteal Artery with Uncoated Balloons and Paclitaxel-Coated Balloons-A Pooled Analysis of Four Randomized Controlled Multicenter Trials.
Cardiovasc Intervent Radiol. 2019; 42(7):949-955 [PubMed] Related Publications
PURPOSE: In view of a recent meta-analysis reporting increased mortality following angioplasty with paclitaxel-coated devices in peripheral arteries, we performed a patient-level 2-year mortality analysis based on pooled original data of four randomized controlled trials (THUNDER, FEMPAC, PACIFIER and CONSEQUENT).
METHODS AND RESULTS: Clinical data of four randomized controlled trial were pooled to assess 2-year mortality following paclitaxel-coated balloon (PCB) angioplasty compared to angioplasty without paclitaxel (control group). A logistic regression model was applied to identify potential predictors of mortality. At two years, 13 of 185 (7.0%) patients had died in the control group and 16/184 (8.7%) in the PBC group, p = 0.55. Kaplan-Meier analysis revealed no significant difference from all-cause death at 2 years (log rank p = 0.54). Causes of death were well balanced between the groups with no pattern or trend in favour of any specific causes in the PBC group. Logistic regression revealed that treatment groups (controls or PBC) were not a predictor of 2-year mortality. The only predictor for mortality was patient age ≥ 75 years. The delivered paclitaxel doses per patient were not significantly different in patients that died and those who did not die during the 24-month follow-up (5.300 ± 4.224 μg vs. 6.248 ± 4.629 μg, p = 0.433).
CONCLUSIONS: Based on original patient-level data of four pooled randomized controlled trials, we found no increase in 2-year mortality in patients treated with PCB compared to control patients treated with uncoated balloons. Causes of death were well balanced between PCB and control patients.

Nakashima K, Akamatsu H, Murakami H, et al.
Carboplatin Plus Nab-paclitaxel in Performance Status 2 Patients With Advanced Non-small-cell Lung Cancer.
Anticancer Res. 2019; 39(3):1463-1468 [PubMed] Related Publications
BACKGROUND/AIM: This phase I/II study aimed at assessing the efficacy of combination therapy with carboplatin (CBDCA) on day 1 and nab-paclitaxel (Nab-PTX) on days 1 and 8 of a 21-day cycle in performance status (PS) 2 patients with non-small-cell lung cancer (NSCLC).
PATIENTS AND METHODS: PS 2 patients with NSCLC were enrolled into a phase I study using a 3 + 3 design. Once the recommended phase II dose (RP2D) was established, the patients were enrolled into phase II.
RESULTS: Based on the phase I findings, the RP2D was determined as CBDCA area under the curve 6 mg/ml/min and Nab-PTX 100 mg/m
CONCLUSION: CBDCA plus Nab-PTX therapy is a promising treatment strategy for PS 2 patients with NSCLC.

Ma Y, Lai W, Zhao M, et al.
Plastin 3 down-regulation augments the sensitivity of MDA-MB-231 cells to paclitaxel via the p38 MAPK signalling pathway.
Artif Cells Nanomed Biotechnol. 2019; 47(1):685-695 [PubMed] Related Publications
Plastin 3 (PLS3) overexpression may serve as a marker for predicting chemotherapeutic outcomes in drug-resistant cancer cells, but the mechanism is unclear. Herein, we show that the down-regulation of PLS3 by PLS3 gene silencing augments the sensitivity of MDA-MB-231 triple-negative breast cancer cells to paclitaxel. Interestingly, a low concentration of paclitaxel was able to induce strong apoptosis in the PLS3-silenced cells. Further study revealed that p38 MAPK signalling was responsible for the increased sensitivity to paclitaxel in these cells, as the p38 MAPK inhibitor SB203580 impaired the changes mediated by PLS3 down-regulation in response to paclitaxel. Therefore, our study identifies PLS3 as a potential target for enhancing the p38 MAPK-mediated apoptosis induced by paclitaxel. Unlike paclitaxel, Abraxane was unable to induce strong apoptosis in the PLS3-silenced cells. As PLS3 was found to be involved in the process of endocytosis in breast cancer cells, the reliance of cellular Abraxane uptake on this process may render it not as efficient as paclitaxel in PLS3-depleted tumour cells. The finding that PLS3 could be a critical regulator of paclitaxel sensitivity may have important implications for breast cancer chemotherapy.

Sookram J, Zheng A, Linden KM, et al.
Epigenetic therapy can inhibit growth of ovarian cancer cells and reverse chemoresistant properties acquired from metastatic omentum.
Int J Gynaecol Obstet. 2019; 145(2):225-232 [PubMed] Related Publications
OBJECTIVE: To examine the cytotoxicity of epigenetic drugs independently and in combination with chemotherapy on ovarian cancer cells Caov-3, and to investigate their ability to acquire chemoresistance in omental microenvironments and whether epigenetic drugs can counteract this chemoresistance.
METHODS: A pilot study was conducted in Cooper University Hospital, NJ, USA from August 1 to October 31, 2017, among women undergoing surgeries for uterine and ovarian cancer. Cytotoxicity assays using IC
RESULTS: Three women met the eligibility criteria and were included in the study. Epigenetic drugs alone or in combination with chemotherapy showed 85%-94% increased cytotoxicity against Caov-3 (P≤0.005). Metastatic OASCs conditioned medium showed up to 27-fold increase in tumorigenic factors and promoted chemoresistance (28%-35%; P < 0.050) against chemotherapy. Epigenetic therapy resulted in up to a 40-fold reversal in this chemoresistance.
CONCLUSION: Epigenetic therapies could have an important role in treating a subgroup of ovarian cancer patients that demonstrate resistance to first-line chemotherapy.

Disclaimer: This site is for educational purposes only; it can not be used in diagnosis or treatment.

[Home]    Page last updated: 02 September, 2019     © CancerIndex, Established 1996