Cancer is becoming a severe health problem internationally and is one of the most deadly diseases (Siegel et al., 2016). Conventional cancer therapy, especially chemotherapy, provides limited efficacy by DNA damage (Li et al., 2017), but has the problems of formidable side effects and drug resistance. To discover novel potent and safe chemotherapeutic agents or seek better curative methods, medicinal chemists, pharmaceutists and pharmacologists have completed many investigations. Artemisinin (ART), bearing a peroxide bridge in its sesquiterpene lactone structure, was extracted and separated from Artemisia annua L. (sweet wormwood), which has been used for treatment of fevers and chills as one of the famous Chinese traditional medicines for thousands of years (Klayman, 1985 Li and Wu, 2003 Cui and Su, 2009 Tu, 2016). ART can be reduced to dihydroartemisinin (DHA) by using sodium borohydride in high yields. Thus, this compound was used as a starting material to prepare the first-ge... See full list on The antitumor activity of ARTs has attracted extensive attention (Firestone and Sundar, 2009 Crespo-Ortiz and Wei, 2012 Frohlich et al., 2016 Wong et al., 2017 Zhang Y. et al., 2ease efficacy and reduce toxi of ARTs, new design strategies for anticancer candidates based on ARTs have been developed. These strategies were raised by researchers from different fields. Medicinal chemists focus more on chemical structural modification to develop novel derivatives whereas pharmacists are more interested in formulation improvement. In our review, we elaborate these novel strategies by focusing on developing novel ART derivatives and manufacturing ART o-formulations as well as combining ARTs with other drugs for cancer therapy. See full list on We searched for clinical trials of ARTs at . and in PubMed. search results by keywords “cancer” and “artesunate” show that some clinical trials of ARS have entered phase II status in recent years. Different modes of administration are used for different cancers. However, no solid final results can be seen yet. In Pubmed, there are only 3 studies in the last 3 years. We summarize the latest research results in 2019 because some previous clinical studies in dogs and humans have been comprehensively reviewed by Efferth and Zhang et al. (Efferth, 2017b Zhang Y. et al., 2018). Recent clinical studies for treating cancer focus on ARS. The results showed dose-limiting toxicities could be seen at dosages of 12, 18 and 25 mg/kg by intravenous ARS in patients with advanced solid tumor maligcies and the maximum tolerated dose was 18 mg/kg using day1/day8, 3-week cycle of administration (Deeken et al., 2018). The adverse events of auditory and vestibular... See full list on ARTs which are already established as safe drugs for treating mia, possess a host of advantages that make them worthy of development as novel anticancer agents. They differ from available anticancer drugs because of the characteristics of high selectivity and effica against multiple cancers in cell and biological models as well as more sensitivity to chemoradiotherapy and less susceptibility to resistance. In this review, we summarized novel cancer therapeutic approaches based on ARTs, the latest molecular mechanisms of action and clinical studies. As a whole, ARTs have great potential to be used in clinical oncology, but there are still many problems to be solved. First, because of poor solubility, short half-life, low bioavailability and toxi of ARTs, developing novel derivatives and odrugs were applied to solve these problems. However, despite the cost savings in drug development by structural modification of ARTs to obtain candidates, updated preclinical and clini... See full list on CX and XY conceived, designed, drafted the manuscript, and amended the paper. HZ designed the figures and tables. LM collected the related research articles. All authors contributed to the article and approved the submitted version. See full list on This work was supported by the Scientific Research Project of Educ (17C0973) to CX and the National Natural Science Foundation of China ) the Key Laboratory of Study and Discovery of Small Ta, Normal University (2017TP1020) and Hug High-Level Talent Innovation Team (2018RS3072) to XY. See full list on The authors declare that the research was conducted in the absence of any commercial or ficial relationships that could be construed as a potential conflict of interest. See full list on Akt, protein kinase B Bak, Bcl-2 homologous antagonist/killer Bcl-2, B cell lymphoma-2 Bax, Bcl-2–associated X protein PI3K, phosphatidylinositol 3-kinase mTOR, mammalian target of rapamycin LC3, light chain 3 CaMKK2, Ca2+/calmodulin-dependent kinase kinase 2 ULK1, unc-51 like autophagy activating kinase 1 PI3KC3, class III phosphatidylinositol 3-kinase T-bet, T-box expressed in T cells MEK, MAPK - mitogen activated protein kinase ERK, extracellular signal-regulated kinase Nrf-2, nuclear factor (erythroid‐derived 2)‐like 2 VEGF, vascular endothelial growth factor JNK, c-Jun-N-terminal kinase γ-H2AX, phosphorylated histone H2AX DSB, double-strand break IFI 16, Interferon-inducible 16 IL, interleukin ATF4, activating transcription factor 4 CHOP, C/EBP homologous protein CHAC1, cation transport regulator-like protein 1 ALDH1, aldehyde dehydrogenase-1. See full list on
Get Price
search