Search

Chemotherapy-induced nausea and vomiting (CINV) is one of the commonest side-effects among cancer patients. However, there is lacking of hierarchical evidences comparing different antiemetics against highly emetogenic chemotherapy. Therefore, we conducted a network meta-analysis to investigate their comparative efficacy and tolerability. Randomized controlled trials that compared different antiemetic categories for adult highly emetogenic chemotherapy were included after searching PubMed, Web of Science, Embase and Cochrane Central. Acute-phase no emesis and no nausea were identified as primary endpoints. We made pairwise and hierarchical calculations by random-effects model. Effect sizes were presented by odds ratio and 95% confidential interval. Subgroup analysis was additionally performed. 143 randomized trials were included into pooled analysis, containing 22,776 patients and 18 antiemetic categories. 5-HT3 RA plus corticosteroid plus NK-1 RA plus other (5CNO) displayed best protection against both acute emesis (SUCRA: 99.7%) and nausea (95.6%). 5CNO (99.7%) and 5-HT3 RA plus corticosteroid plus other (5CO, 85.3%) topped subgroup hierarchies for no-naivety and anthracycline plus cyclophosphamide (AC)-based studies. On the other hand, 5-HT3 RA plus dopamine RA plus other (5DO) may be best fit for delayed emesis (92.0%) and nausea (92.7%). Subgroups featuring no-naivety and AC-based trials preferred 5DO (91.9%) and 5CN (88.6%), respectively. In addition, dopamine RA plus other (DO) had the lowest incidence of TRAE in most circumstances, except for AC-based subgroup where corticosteroid plus dopamine RA plus other (CDO) preponderated (69.2%). 5CNO and 5DO should be considered as first-line regimens against highly emetogenic chemotherapy induced acute and delayed CINV, respectively. [ABSTRACT FROM AUTHOR]

Chemotherapy is a major therapeutic option for cancer patients. However, its effectiveness is challenged by chemodrugs' intrinsic pathological interactions with residual cancer cells. While inducing cancer cell death, chemodrugs enhance cancer stemness, invasiveness, and drug resistance of remaining cancer cells through upregulating cyclooxygenase‐2/prostaglandin‐E2 (COX‐2/PGE2) signaling, therefore facilitating cancer repopulation and relapse. Toward tumor eradication, it is necessary to improve chemotherapy by abrogating these chemotherapy‐induced effects. Herein, redox‐responsive, celecoxib‐modified mesoporous silica nanoparticles with poly(β‐cyclodextrin) wrapping (MSCPs) for sealing doxorubicin (DOX) are synthesized. Celecoxib, an FDA‐approved COX‐2 inhibitor, is employed as a structural and functional element to confer MSCPs with redox‐responsiveness and COX‐2/PGE2 inhibitory activity. MSCPs efficiently codeliver DOX and celecoxib into the tumor location, minimizing systemic toxicity. Importantly, through blocking chemotherapy‐activated COX‐2/PGE2 signaling, MSCPs drastically enhance DOX's antitumor activity by suppressing enhancement of cancer stemness and invasiveness as well as drug resistance induced by DOX‐based chemotherapy in vitro. This is also remarkably achieved in three preclinical tumor models in vivo. DOX‐loaded MSCPs effectively inhibit tumor repopulation by blocking COX‐2/PGE2 signaling, which eliminates DOX‐induced expansion of cancer stem‐like cells, distant metastasis, and acquired drug resistance. Thus, this drug delivery nanosystem is capable of effectively suppressing tumor repopulation and has potential clinical translational value. Redox‐responsive, celecoxib‐modified mesoporous silica nanoparticle‐based drug delivery nanosystems (MSCPs) are fabricated to deliver doxorubicin (DOX) toward eradicating tumor relapse. MSCPs efficiently codeliver DOX and celecoxib to the tumor location, inhibit tumor growth, and suppress tumor repopulation by blocking the COX‐2/PGE2 pathway, which eliminates DOX‐induced expansion of cancer stem‐like cells, distant metastasis, and acquired drug resistance. [ABSTRACT FROM AUTHOR]

Chemotherapy effectiveness is greatly challenged by chemodrugs' intrinsic pathological interactions with tumor cells, which enhance cancer stemness, invasiveness and acquired drug resistance. In article number 1801987, Guobin Wang, Zheng Wang, Lin Wang, and co‐workers construct a redox‐responsive, celecoxib‐modified nanosystem that efficiently enhances doxorubicin‐based chemotherapy and suppresses cancer repopulation by abrogating doxorubicin‐induced enhancement of cancer stemness, metastasis and drug resistance. [ABSTRACT FROM AUTHOR]

Multidrug resistance (MDR) is a key issue accounting for ineffectiveness of cancer chemotherapy. Numerous multifunctional nanocarriers have been developed to increase drug delivery efficacy and inhibit drug efflux for overcoming cancer drug resistance. However, limited success has been achieved in clinic because of nanocarriers' complicated multi-step fabrication procedures and their undesired side toxicity as well as potential immunogenicity. Here, hyaluronic acid (HA) functionalized extracellular vesicles (EVs) are generated as natural vehicles to efficiently deliver doxorubicin (DOX) and reverse MDR. The EVs isolated from noncancerous HEK293T cells (hEVs) reduce P-glycoprotein (P-gp) expression in drug resistant MCF7/ADR cells. To acquire tumor-targeting capability, hEVs are modified with lipidomimetic chains-grafted HA (lipHA) by a simple incubation. Owing to CD44-mediated cancer-specific targeting and P-gp suppressive capability, the HA-functionalized hEVs (lipHA-hEVs) remarkably promote the intracellular DOX accumulation in drug resistant breast cancer cells. In preclinical MDR tumor models, lipHA-hEVs deeply penetrate into tumor tissue and effectively transport DOX into tumor local, while eliminating DOX's systemic toxicity. Importantly, DOX@lipHA-hEVs inhibited MDR tumor growth by 89% and extend animal survival time by approximately 50%. Thus, our engineered tumor-targeting hEVs are promising natural carriers for overcoming cancer MDR. [ABSTRACT FROM AUTHOR]