Paclitaxel and docetaxel are among the most widely used chemotherapeutic drugs against various types of cancer. However, these drugs cause undesirable side effects as well as drug resistance. Therefore, it is essential to develop next-generation taxoid anticancer agents with better pharmacological properties and improved activity especially against drug-resistant and metastatic cancers. The SAR studies by the authors have led to the development of numerous highly potent novel second- and third-generation taxoids with systematic modifications at the C-2, C-10, and C-3' positions. The third-generation taxoids showed virtually no difference in potency against drug-resistant and drug-sensitive cell lines. Some of the next-generation taxoids also exhibited excellent potency against cancer stem cells. This account summarizes concisely investigations into taxoids over 25 years based on a strong quest for the discovery and development of efficacious next-generation taxoids. Discussed herein are SAR studies on different types of taxoids, a common pharmacophore proposal for microtubule-stabilizing anticancer agents and its interesting history, the identification of the paclitaxel binding site and its bioactive conformation, characteristics of the next-generation taxoids in cancer cell biology, including new aspects of their mechanism of action, and the highly efficacious tumor-targeted drug delivery of potent next-generation taxoids.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5869464 | PMC |
| http://dx.doi.org/10.1021/acs.jnatprod.7b01012 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Ivermectin Enhances Paclitaxel Efficacy by Overcoming Resistance Through Modulation of in Non-small Cell Lung Cancer.
Anticancer Res
December 2024
Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
Background/aim: Chemoresistance to paclitaxel (PTX) significantly ameliorates therapeutic efficacy in patients with non-small cell lung cancer (NSCLC), especially in advanced stages, deteriorating the progression free and overall survival rates. One of the critical mechanisms contributing to drug resistance is the excretion of PTX from target cells via efflux pumps. Ivermectin was developed as a bactericidal agent against parasites; however, it has recently been shown to inhibit the proliferation of human cancer cells.
View Article and Find Full Text PDF[A real-world study of first-line albumin-bound paclitaxel in the treatment of advanced pancreatic cancer in China].
Zhonghua Zhong Liu Za Zhi
November 2024
Department of Oncology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing210008, China.
To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues. From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS).
View Article and Find Full Text PDFConversion therapy with chemoimmunotherapy induced pCR in a stage IV lung squamous cell carcinoma patient harboring exon 20 insertion.
Hum Vaccin Immunother
December 2024
Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
This case study details an innovative conversion therapy strategy in a 58-year-old Asian male with baseline stage cTNM advanced lung squamous cell carcinoma (SCC) harboring a rare exon 20 insertion mutation with concurrent high PD-L1 expression who achieved a pathologic complete response (pCR) after preoperative immunotherapy plus chemotherapy. The patient initially presented with coughing and bloody sputum and was comprehensively diagnosed via PET/CT scanning, bronchoscopic biopsy and next-generation sequencing. After four cycles of platinum‒paclitaxel chemotherapy plus immunotherapy with pembrolizumab (a PD-1 blockade), significant primary tumor shrinkage and the disappearance of oligometastasis in the right adrenal gland were discovered via CT scans.
View Article and Find Full Text PDFGenomic and transcriptomic profiling of pre- and postneoadjuvant chemotherapy triple negative breast cancer tumors.
Cancer Sci
December 2024
Tokyo Metropolitan Cancer and Infectious Disease Center, Komagome Hospital, Bunkyo-ku, Tokyo, Japan.
Article Synopsis
- Neoadjuvant treatment with microtubule inhibitors (MTIs) for triple negative breast cancer (TNBC) is not well understood, prompting a study that analyzed tumor samples to correlate genetic mutations with treatment response.
- The study found that tumors with high homologous recombination deficiency (HRD) and specific mutations (like BRCA2) had higher rates of complete response to MTIs like eribulin and paclitaxel.
- Transcriptomic profiling highlighted FGFR2 downregulation as a critical gene linked to treatment response and identified a significant pathway (glycan degradation) that could influence resistance to these therapies in TNBC patients.*
Real-world Efficacy and Safety of Low-Dose Abiraterone With Food and Standard-Dose Abiraterone in De Novo Metastatic Hormone-Sensitive Prostate Cancer: A Retrospective Analysis.
Clin Genitourin Cancer
December 2024
Quansu Pathology Department, National Cancer Hospital, Hanoi, Vietnam.
Background: The standard treatment for de novo metastatic hormone-sensitive prostate cancer (mHSPC) involves androgen deprivation therapy (ADT) combined with next-generation hormonal agents and/or docetaxel. While the standard dose (STD) of abiraterone is 1,000 mg administered while fasting, recent evidence suggests that a low dose (LOW) of 250 mg taken with a low-fat meal may achieve comparable pharmacokinetic outcomes.
Objectives: This study aimed to evaluate the failure-free survival (FFS) and safety of LOW and STD in de novo high-risk mHSPC patients.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!