-
Biomedicine & Pharmacotherapy =... May 2023Paclitaxel, a compound naturally occurring in yew, is a commonly used drug for the treatment of different types of cancer. Unfortunately, frequent cancer cell resistance... (Review)
Review
Paclitaxel, a compound naturally occurring in yew, is a commonly used drug for the treatment of different types of cancer. Unfortunately, frequent cancer cell resistance significantly decreases its anticancer effectivity. The main reason for the resistance development is the paclitaxel-induced phenomenon of cytoprotective autophagy occurring by different mechanisms of action in dependence on a cell type and possibly even leading to metastases. Paclitaxel also induces autophagy in cancer stem cells, which greatly contributes to tumor resistance development. Paclitaxel anticancer effectivity can be predicted by the presence of several autophagy-related molecular markers, such as tumor necrosis factor superfamily member 13 in triple-negative breast cancer or cystine/glutamate transporter encoded by the SLC7A11 gene in ovarian cancer. Nevertheless, the undesired effects of paclitaxel-induced autophagy can be eliminated by paclitaxel co-administration with autophagy inhibitors, such as chloroquine. Interestingly, in certain cases, it is worthy of potentiating autophagy by paclitaxel combination with autophagy inducers, for instance, apatinib. A modern strategy in anticancer research is also to encapsulate chemotherapeutics into nanoparticle carriers or develop their novel derivatives with improved anticancer properties. Hence, in this review article, we summarize not only the current knowledge of paclitaxel-induced autophagy and its role in cancer resistance but mainly the possible drug combinations based on paclitaxel and their administration in nanoparticle-based formulations as well as paclitaxel analogs with autophagy-modulating properties.
Topics: Female; Humans; Paclitaxel; Antineoplastic Agents, Phytogenic; Apoptosis; Ovarian Neoplasms; Autophagy; Cell Line, Tumor; Drug Resistance, Neoplasm
PubMed: 36889112
DOI: 10.1016/j.biopha.2023.114458 -
Advanced Drug Delivery Reviews Dec 2017Paclitaxel (PTX) is one of the three most widely used chemotherapeutic agents, together with doxorubicin and cisplatin, and is first or second line treatment for several... (Review)
Review
Paclitaxel (PTX) is one of the three most widely used chemotherapeutic agents, together with doxorubicin and cisplatin, and is first or second line treatment for several types of cancers. In 2000, Taxol, the conventional formulation of PTX, became the best-selling cancer drug of all time with annual sales of 1.6 billion. In 2005, the introduction of the albumin-based formulation of PTX, known as Abraxane, ended Taxol's monopoly of the PTX market. Abraxane's ability to push the Taxol innovator and generic formulations aside attracted fierce competition amongst competitors worldwide to develop their own unique, new and improved formulation of PTX. At this time there are at least 18 companies focused on pre-clinical and/or clinical development of nano-formulations of PTX. These pharmaceutical companies are investing substantial capital to capture a share of the lucrative global PTX market. It is hoped that any formulation that dominates the market will result in tangible benefits to patients in terms of both survival and quality of life. Given all of this activity, here we address the question: Who is going to win the battle of "nano" paclitaxel?
Topics: Animals; Humans; Nanoparticles; Neoplasms; Paclitaxel
PubMed: 28257998
DOI: 10.1016/j.addr.2017.02.003 -
New Biotechnology May 2014Plants are capable of producing a wide variety of secondary metabolites which have a diverse range of functions that can be exploited for medicinal purposes; for... (Review)
Review
Plants are capable of producing a wide variety of secondary metabolites which have a diverse range of functions that can be exploited for medicinal purposes; for example, paclitaxel is a major anti-cancer drug found in the bark of Taxus spp. There are however supply issues as the compound is only found at low concentrations (0.05%) within the plant. The complex paclitaxel biosynthetic pathway makes chemical synthesis non-commercially viable; therefore alternative biotechnological sources have been explored for production including heterologous expression systems and plant cell culture.
Topics: Biosynthetic Pathways; Humans; Paclitaxel
PubMed: 24614567
DOI: 10.1016/j.nbt.2014.02.010 -
Pharmacogenomics May 2010The microtubule-stabilizing drug paclitaxel is a cytotoxic agent widely used for the treatment of a variety of tumor types. Since its introduction to the clinic,... (Review)
Review
The microtubule-stabilizing drug paclitaxel is a cytotoxic agent widely used for the treatment of a variety of tumor types. Since its introduction to the clinic, modifications to the administration schedule and treatments for hypersensitivity reactions and neutropenia have significantly improved paclitaxel therapy. On the other hand, severe neurotoxicity and lack of response are still clinical challenges. During the last decade a deeper knowledge of paclitaxel pharmacokinetics and pharmacodynamics has been achieved, together with an in-depth characterization of genes involved in its elimination and therapeutic response. Pharmacogenetic studies aimed at the identification of paclitaxel outcome biomarkers have been performed, however, further efforts will be required to successfully integrate these and future results to provide the basis for personalized paclitaxel therapy.
Topics: Clinical Trials as Topic; Humans; Microtubules; Neoplasms; Paclitaxel; Pharmacogenetics
PubMed: 20415548
DOI: 10.2217/pgs.10.32 -
Casopis Lekaru Ceskych Jun 1996The paclitaxel (TAXOL); Bristol-Myers Squibb Company) represents first agent from novel class of antineoplastic drugs--taxanes to enter routine clinical practice.... (Review)
Review
The paclitaxel (TAXOL); Bristol-Myers Squibb Company) represents first agent from novel class of antineoplastic drugs--taxanes to enter routine clinical practice. Paclitaxel interferes with microtubular polymerization by promoting abnormal assembly of microtubules and inhibiting their subsequent disassembly. Pharmacokinetics of paclitaxel has been intensively studied. There are indications for nonlinear pharmacokinetics when paclitaxel is administered as a short infusion and at higher doses. Neurotoxicity, mucositis, and leukopenia correlate with some pharmacokinetic parameters. The clinical development of paclitaxel was initially hampered by hypersensitivity reactions. Current dosage regiments with premedication reduced the incidence of these events to 3%. The major dose-limiting adverse effect of paclitaxel is neutropenia. Significant activities were reported especially in patients with advanced ovarian, breast, non-small cell lung cancer (NSCLC), head and neck cancer and in other types of tumours. Long-term follow-up will also allow the effects of the drug on patient survival to be determined. At present combination of Taxol (paclitaxel) with cisplatin clearly improves the duration of progression-free survival and of overall survival compared with cyclophosphamide and cisplatin in women ovarian cancer. Recently was TAXOL (paclitaxel) registered in Czech republic for treatment of patients with advanced metastatic ovarian carcinoma and in patients with metastatic breast cancer after failure of the standard therapy.
Topics: Antineoplastic Agents, Phytogenic; Humans; Paclitaxel
PubMed: 8706079
DOI: No ID Found -
Critical Reviews in Oncology/hematology Mar 2007Paclitaxel is one of the most widely used and effective anticancer drugs. Paclitaxel's clinical utility spans many tumor sites, including treatment of ovarian, breast,... (Review)
Review
Paclitaxel is one of the most widely used and effective anticancer drugs. Paclitaxel's clinical utility spans many tumor sites, including treatment of ovarian, breast, lung, head and neck, and unknown primary cancers. As is the case with most chemotherapy drugs, paclitaxel is administered empirically with little individualization of dose other than adjustment for body surface area. Metabolism of the drug is predominantly by the liver by cytochromes P450 2C8 and 3A4. Recent evidence points to the presence of polymorphisms in these enzymes. The clinical relevance of these polymorphisms is not yet fully explored, though they are expected to be key in fulfilling the ultimate goal of individualized dosing of paclitaxel. Here we review the pharmacology of paclitaxel and consider the possible effects pharmacogenetics may have on paclitaxel therapy.
Topics: Antineoplastic Agents, Phytogenic; Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 CYP2C8; Cytochrome P-450 Enzyme System; Humans; Paclitaxel; Polymorphism, Genetic
PubMed: 17092739
DOI: 10.1016/j.critrevonc.2006.09.006 -
Drug Design, Development and Therapy 2015Albumin-bound paclitaxel (nab-paclitaxel) is a solvent-free formulation of paclitaxel that was initially developed more than a decade ago to overcome toxicities... (Review)
Review
Albumin-bound paclitaxel (nab-paclitaxel) is a solvent-free formulation of paclitaxel that was initially developed more than a decade ago to overcome toxicities associated with the solvents used in the formulation of standard paclitaxel and to potentially improve efficacy. Nab-paclitaxel has demonstrated an advantage over solvent-based paclitaxel by being able to deliver a higher dose of paclitaxel to tumors and decrease the incidence of serious toxicities, including severe allergic reactions. To date, nab-paclitaxel has been indicated for the treatment of three solid tumors in the USA. It was first approved for the treatment of metastatic breast cancer in 2005, followed by locally advanced or metastatic non-small-cell lung cancer in 2012, and most recently for metastatic pancreatic cancer in 2013. Nab-paclitaxel is also under investigation for the treatment of a number of other solid tumors. This review highlights key clinical efficacy and safety outcomes of nab-paclitaxel in the solid tumors for which it is currently indicated, discusses ongoing trials that may provide new data for the expansion of nab-paclitaxel's indications into other solid tumors, and provides a clinical perspective on the use of nab-paclitaxel in practice.
Topics: Albumin-Bound Paclitaxel; Albumins; Animals; Antineoplastic Agents, Phytogenic; Chemistry, Pharmaceutical; Diffusion of Innovation; Forecasting; Humans; Nanomedicine; Nanoparticles; Paclitaxel; Technology, Pharmaceutical
PubMed: 26244011
DOI: 10.2147/DDDT.S88023 -
Cancer Practice 1994Paclitaxel, a compound derived from the bark of the Pacific yew, Taxus brevifolia, is an antimitotic cytotoxic agent with a mechanism of action different from other... (Review)
Review
Paclitaxel, a compound derived from the bark of the Pacific yew, Taxus brevifolia, is an antimitotic cytotoxic agent with a mechanism of action different from other antimitotics such as vincristine and vinblastine. Instead of causing disassembly of microtubules, paclitaxel forms extremely stable and nonfunctional microtubules, which causes inhibition of many cell functions and the interruption of the cell cycle. Procurement of paclitaxel has raised environmental concerns, leading researchers to explore a variety of approaches to obtain the drug: extraction from yew needles of a paclitaxel precursor that can be converted to paclitaxel, genetic manipulation of plants to increase yield, propagation of yew trees, semisynthesis, total chemical synthesis, and paclitaxel-producing fungus. Clinical trials involving paclitaxel have demonstrated antineoplastic effects in several classically refractory tumors: ovarian cancer, breast cancer, non-small-cell lung cancer, and head and neck tumors. Several toxic effects have been attributed to paclitaxel, including hypersensitivity reactions, cardiotoxicities, neutropenia, peripheral neuropathy, mucositis, gastrointestinal toxicities, alopecia, arthralgias, and myalgias. Clinical implications for these toxicities are addressed.
Topics: Clinical Trials as Topic; Environmental Health; Humans; Neoplasms; Paclitaxel
PubMed: 7914453
DOI: No ID Found -
Materials Science & Engineering. C,... Oct 2018Localised and targeted potential of nanocarrier for the eminent anticancer agent paclitaxel (PTX) could provide a great platform towards improvement of efficacy with... (Review)
Review
Localised and targeted potential of nanocarrier for the eminent anticancer agent paclitaxel (PTX) could provide a great platform towards improvement of efficacy with reduction in associated toxicities, whereas incorporation of TPGS could further facilitate delivery in MDR through alteration of its inherent physicochemical properties. Current article therefore puts into perspective on nanocarrier-based recent researches of PTX with special stress towards TPGS-nanoparticle-mediated delivery in the improvement of cancer treatment and then accompanied with the discussion on distinct influence of the fabrication process. Such dynamic fabrications of the nanoparticulate therapy stimulate cellular interaction with frontier area for future research in tumor targeting potential.
Topics: Animals; Drug Delivery Systems; Humans; Nanoparticles; Nanotechnology; Neoplasms; Paclitaxel; Vitamin E
PubMed: 30033322
DOI: 10.1016/j.msec.2018.05.054 -
Cancer Jun 2000Compelling evidence indicates that paclitaxel kills cancer cells through the induction of apoptosis. Paclitaxel binds microtubules and causes kinetic suppression... (Review)
Review
BACKGROUND
Compelling evidence indicates that paclitaxel kills cancer cells through the induction of apoptosis. Paclitaxel binds microtubules and causes kinetic suppression (stabilization) of microtubule dynamics. The consequent arrest of the cell cycle at mitotic phase has been considered to be the cause of paclitaxel-induced cytotoxicity. However, the biochemical events, downstream from paclitaxel's binding to microtubules, that lead to apoptosis are not well understood.
METHODS
The authors examined recent scientific literature about the mechanisms by which paclitaxel exerts cytotoxicity.
RESULTS
In addition to an arrest of the cell cycle at the mitotic phase in paclitaxel-treated cells, recent discoveries of activation of signaling molecules by paclitaxel and paclitaxel-induced transcriptional activation of various genes indicate that paclitaxel initiates apoptosis through multiple mechanisms. The checkpoint of mitotic spindle assembly, aberrant activation of cyclin-dependent kinases, and the c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) are shown to be involved in paclitaxel-induced apoptosis. Consistent with observations that microtubules of different status (e.g., cytoskeletal microtubules vs. mitotic spindles) have different sensitivity to paclitaxel, the concentration of paclitaxel appears to be the major determinant of its apoptogenic mechanisms.
CONCLUSIONS
Advances in research of the cell cycle and apoptosis have extended our understanding of the mechanisms of paclitaxel-induced cell death. Further elucidation of resistance and enhancement of paclitaxel-induced apoptosis should expedite the development of better paclitaxel-based regimens for cancer therapy.
Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Cell Cycle; Cell Death; Gene Expression; Humans; Microtubules; Paclitaxel
PubMed: 10861441
DOI: 10.1002/1097-0142(20000601)88:11<2619::aid-cncr26>3.0.co;2-j