Colorectal cancer (CRC) is often diagnosed at an advanced stage when tumor cell dissemination has taken place. Chemo- and targeted therapies provide only a limited increase of overall survival for these patients. The major reason for clinical outcome finds its origin in therapy resistance. Escape mechanisms to both chemo- and targeted therapy remain the main culprits. Here, we evaluate major resistant mechanisms and elaborate on potential new therapies. Amongst promising therapies is α-amanitin antibody-drug conjugate targeting hemizygous p53 loss. It becomes clear that a dynamic interaction with the tumor microenvironment exists and that this dictates therapeutic outcome. In addition, CRC displays a limited response to checkpoint inhibitors, as only a minority of patients with microsatellite instable high tumors is susceptible. In this review, we highlight new developments with clinical potentials to augment responses to checkpoint inhibitors.

Multidrug resistance is a major challenge to cancer chemotherapy. The multidrug resistance phenotype is associated with the overexpression of the adenosine triphosphate (ATP)-driven transmembrane efflux pumps in cancer cells. Here, we report a lipid membrane-coated silica-carbon (LSC) hybrid nanoparticle that targets mitochondria through pyruvate, to specifically produce reactive oxygen species (ROS) in mitochondria under near-infrared (NIR) laser irradiation. The ROS can oxidize the NADH into NAD+ to reduce the amount of ATP available for the efflux pumps. The treatment with LSC nanoparticles and NIR laser irradiation also reduces the expression and increases the intracellular distribution of the efflux pumps. Consequently, multidrug-resistant cancer cells lose their multidrug resistance capability for at least 5 days, creating a therapeutic window for chemotherapy. Our in vivo data show that the drug-laden LSC nanoparticles in combination with NIR laser treatment can effectively inhibit the growth of multidrug-resistant tumors with no evident systemic toxicity.

Kaempferol, also known as kaempferol-3 or kaempferide, is a flavonoid compound that naturally occurs in tea, as well as numerous common vegetables and fruits, including beans, broccoli, cabbage, gooseberries, grapes, kale, strawberries, tomatoes, citrus fruits, brussel sprouts, apples and grapefruit. The present review mainly summarizes the application of kaempferol in treating diseases and the underlying mechanisms that are currently being studied. Due to its anti-inflammatory properties, it may be used to treat numerous acute and chronic inflammation-induced diseases, including intervertebral disc degeneration and colitis, as well as post-menopausal bone loss and acute lung injury. In addition, it has beneficial effects against cancer, liver injury, obesity and diabetes, inhibits vascular endothelial inflammation, protects the cranial nerve and heart function, and may be used for treating fibroproliferative disorders, including hypertrophic scar.

In this study, the secondary sequencing was used to profile circRNA expression in the tissue samples from three CRC patients with liver metastasis and three matched CRC patients. After verified some candidates in another 40 CRC and CRC-m samples by qRT-PCR, we further demonstrated that circRNA_0001178 and circRNA_0000826 were significantly upregulated in CRC-m tissues, and both of them had the potential for diagnosing liver metastases from colorectal cancer. Finally, the networks of circRNA-miRNA-mRNA base on these two circRNAs were constructed respectively. This study showed that differentially expressed circRNAs were existed between the tissue samples from colorectal cancer patients with and without liver metastasis. And also suggested that circRNA_0001178 and circRNA_0000826 may serve as a potential diagnostic biomarker for liver metastases from colorectal cancer.Electronic supplementary materialThe online version of this article (10.1186/s12943-018-0932-8) contains supplementary material, which is available to authorized users.

Dysregulated energetic metabolism has been recently identified as a hallmark of cancer. Although mutations in metabolic enzymes hardwire metabolism to tumourigenesis, they are relatively infrequent in ovarian cancer. More often, cancer metabolism is re-engineered by altered abundance and activity of the metabolic enzymes. Here we identify ubiquitin-specific peptidase 13 (USP13) as a master regulator that drives ovarian cancer metabolism. USP13 specifically deubiquitinates and thus upregulates ATP citrate lyase and oxoglutarate dehydrogenase, two key enzymes that determine mitochondrial respiration, glutaminolysis and fatty acid synthesis. The USP13 gene is co-amplified with PIK3CA in 29.3% of high-grade serous ovarian cancers and its overexpression is significantly associated with poor clinical outcome. Inhibiting USP13 remarkably suppresses ovarian tumour progression and sensitizes tumour cells to the treatment of PI3K/AKT inhibitor. Our results reveal an important metabolism-centric role of USP13, which may lead to potential therapeutics targeting USP13 in ovarian cancers.