Triple-negative breast cancer (TNBC), which accounts for 15-20% of all breast cancers, does not express estrogen receptor (ER) or progesterone receptor (PR) and lacks human epidermal growth factor receptor 2 (HER2) overexpression or amplification. These tumors have a more aggressive phenotype and a poorer prognosis due to the high propensity for metastatic progression and absence of specific targeted treatments. Patients with TNBC do not benefit from hormonal or trastuzumab-based targeted therapies because of the loss of target receptors. Although these patients respond to chemotherapeutic agents such as taxanes and anthracyclines better than other subtypes of breast cancer, prognosis remains poor. A group of targeted therapies under investigation showed favorable results in TNBC, especially in cancers with BRCA mutation. The lipid-lowering statins (3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors), including lovastatin and simvastatin, have been shown to preferentially target TNBC compared with non-TNBC. These statins hold great promise for the management of TNBC. Only with the understanding of the molecular basis for the preference of statins for TNBC and more investigations in clinical trials can they be reformulated into a clinically approved drug against TNBC.

Doxorubicin (DOX), also known as adriamycin, is a DNA topoisomerase II inhibitor and belongs to the family of anthracycline anticancer drugs. DOX is used for the treatment of a wide variety of cancer types. However, resistance among cancer cells has emerged as a major barrier to effective treatment using DOX. Currently, the role of autophagy in cancer resistance to DOX and the mechanisms involved have become one of the areas of intense investigation. More and more preclinical data are being obtained on reversing DOX resistance through modulation of autophagy as one of the promising therapeutic strategies. This review summarizes the recent advances in autophagy-targeting therapies that overcome DOX resistance from in-vitro studies to animal models for exploration of novel delivery systems. In-depth understanding of the mechanisms of autophagy regulation in relation to DOX resistance and development of molecularly targeted autophagy-modulating agents will provide a promising therapeutic strategy for overcoming DOX resistance in cancer treatment.

Cancer stem cells reside in a distinct microenvironment called niche. The reciprocal interactions between cancer stem cells and niche contribute to the maintenance and enrichment of cancer stem cells. In order to simulate the interactions between cancer stem cells and niche, three-dimensional models have been developed. These in vitro culture systems recapitulate the spatial dimension, cellular heterogeneity, and the molecular networks of the tumor microenvironment and show great promise in elucidating the pathophysiology of cancer stem cells and designing more clinically relavant treatment modalites.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with a higher risk in younger women and a poorer prognosis and without targeted therapies available currently. Cancer stem cells (CSCs) are increasingly recognized as the main cause of treatment failure and tumor recurrence. The present paper reports the encapsulation of lovastatin (LV) into cerasomes. Compared with free LV, cerasome-encapsulated LV (C-LV) nanohybrids showed cytotoxicity to MDA-MB-231 CSCs in a dose- and time-dependent manner. Furthermore, intravenous injection of C-LV nanohybrids resulted in a significant tumor size reduction in a dose-dependent manner in xenograft tumors derived from subcutaneous inoculation of MDA-MB-231 cells. Furthermore, histopathological and/or immunohistochemical analysis revealed that C-LV nanohybrids significantly induced mammary gland formation and apoptosis and inhibited angiogenesis, the CSC phenotype, and the epithelial-to-mesenchymal transition in xenograft tumors. Most importantly, C-LV nanohybrids were found to be more effective than free LV in inhibiting the growth of breast cancer xenografts and the stemness properties in vivo. To the best of our knowledge, ours is the first demonstration of nanohybrids for efficient inhibition of CSCs derived from TNBC, offering a new option for the TNBC treatment.

Colorectal cancer (CRC) is the fourth most frequently diagnosed cancer worldwide. Despite the decrease in mortality of CRC patients, further investigation of the molecular pathogenesis of CRC could unveil new therapeutic targets and offer better prognosis predictions, which might direct attention to epigenetic regulators. Methods: Publicly available data from the Gene Expression Omnibus (GEO) database and clinical samples were collected. Bioinformatics methods were used to screen hub genes expressed in CRC. qRT-PCR and Western blotting were used to experimentally determine the expression of one gene of interest, the helicase lymphoid-specific (HELLS) gene, at the RNA and protein levels. Immunohistochemical (IHC) assays were used to correlate the stained HELLS proteins to survival data. Cell proliferation levels were assayed by a CCK-8 kit, a colony formation assay was performed, and flow cytometry was used to quantify the cells at each stage of the cell cycle. Results: A total of 225 overlapping genes were screened, including 14 hub genes. Analysis through a protein-protein interaction (PPI) network and the Gene Ontology database was performed by using the Cytoscape and DAVID online tools, respectively. HELLS RNA and protein expression levels in tumor tissues were 2.09-fold higher and 1.46-fold higher, respectively, than in the peritumoral tissues (p < 0.001, p<0.001). HELLS expression was significantly associated with the T stage (p=0.0027), M stage (p=0.0119), and TNM clinical stage (p = 0.0312) and a higher pathological grade (p=0.049). Highly expressed HELLS was reversibly associated with overall survival (log-rank p = 0.027). HELLS siRNA impaired cell proliferation and colony generation in vitro. HELLS siRNA induced significant G2+M arrest in HT29 and HCT116 cells compared with the respective negative controls (82.29% vs 25.85% and 35.41% vs 15.26%, respectively). Conclusion: Our data revealed that HELLS was significantly upregulated in CRC and correlated with clinicopathological parameters. High expression of HELLS indicated poor prognosis for CRC patients. HELLS knockdown led to impaired cell proliferation, colony generation, and G 2 +M cell cycle arrest.