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The combination of immunotherapy and antiangiogenic agents for the treatment of refractory solid tumor has not been well investigated. Thus, our study aimed to evaluate the efficacy and safety of a new regimen of anlotinib plus PD‐1 inhibitor to treat refractory solid tumor. APICAL‐RST is an investigator‐initiated, open‐label, single‐arm, phase II trial in patients with heavily treated, refractory, metastatic solid tumor. Eligible patients experienced disease progression during prior therapy without further effective regimen. All patients received anlotinib and PD‐1 inhibitor. The primary endpoints were objective response and disease control rates. The secondary endpoints included the ratio of progression‐free survival 2 (PFS2)/PFS1, overall survival (OS) and safety. Forty‐one patients were recruited in our study; 9 patients achieved a confirmed partial response and 21 patients had stable disease. Objective response rate and disease control rate were 22.0% and 73.2% in the intention‐to‐treat cohort, and 24.3% and 81.1% in the efficacy‐evaluable cohort, respectively. A total of 63.4% (95% confidence interval [CI]: 46.9%‐77.4%) of the patients (26/41) presented PFS2/PFS1 >1.3. The median OS was 16.8 months (range: 8.23‐24.4), and the 12‐ and 36‐month OS rates were 62.8% and 28.9%, respectively. No significant association was observed between concomitant mutation and efficacy. Thirty‐one (75.6%) patients experienced at least one treatment‐related adverse event. The most common adverse events were hypothyroidism, hand‐foot syndrome and malaise. This phase II trial showed that anlotinib plus PD‐1 inhibitor exhibits favorable efficacy and tolerability in patients with refractory solid tumor. [ABSTRACT FROM AUTHOR]

Efficient delivery of functional factors into target cells remains challenging. Although extracellular vesicles (EVs) are considered to be potential therapeutic delivery vehicles, a variety of efficient therapeutic delivery tools are still needed for cancer cells. Herein, we demonstrated a promising method to deliver EVs to refractory cancer cells via a small molecule-induced trafficking system. We generated an inducible interaction system between the FKBP12-rapamycin-binding protein (FRB) domain and FK506 binding protein (FKBP) to deliver specific cargo to EVs. CD9, an abundant protein in EVs, was fused to the FRB domain, and the specific cargo to be delivered was linked to FKBP. Rapamycin recruited validated cargo to EVs through protein-protein interactions (PPIs), such as the FKBP-FRB interaction system. The released EVs were functionally delivered to refractory cancer cells, triple negative breast cancer cells, non-small cell lung cancer cells, and pancreatic cancer cells. Therefore, the functional delivery system driven by reversible PPIs may provide new possibilities for a therapeutic cure against refractory cancers. [ABSTRACT FROM AUTHOR]

Epothilone is a natural 16-membered macrolide cytotoxic compound produced by the metabolism of the cellulose-degrading myxobacterium Sorangium cellulosum. This review summarizes results in the study of epothilones against cancer with preclinical results and clinical studies from 2010–2022. Epothilone have mechanisms of action similar to paclitaxel by inducing tubulin polymerization and apoptosis with low susceptibility to tumor resistance mechanisms. It is active against refractory tumors, being superior to paclitaxel in many respects. Since the discovery of epothilones, several derivatives have been synthesized, and most of them have failed in Phases II and III in clinical trials; however, ixabepilone and utidelone are currently used in clinical practice. There is robust evidence that triple-negative breast cancer (TNBC) treatment improves using ixabepilone plus capecitabine or utidelone in combination with capecitabine. In recent years innovative synthetic strategies resulted in the synthesis of new epothilone derivatives with improved activity against refractory tumors with better activities when compared to ixabepilone or taxol. These compounds together with specific delivery mechanisms could be developed in anti-cancer drugs. [ABSTRACT FROM AUTHOR]