Post-translational modification of KRAS: potential targets for cancer therapy.

Aberrant activation of the RAS superfamily is one of the critical factors in carcinogenesis. Among them, KRAS is the most frequently mutated one which has inspired extensive studies for developing approaches to intervention. Although the cognition toward KRAS remains far from complete, mounting evidence suggests that a variety of post-translational modifications regulate its activation and localization.

Multikinase Inhibitor CT-707 Targets Liver Cancer by Interrupting the Hypoxia-Activated IGF-1R-YAP Axis.

Given that Yes-associated protein (YAP) signaling acts as a critical survival input for hypoxic cancer cells in hepatocellular carcinoma (HCC), disruption of YAP function and the maintenance of hypoxia is an attractive way to treat HCC. Utilizing a cell-based YAP-TEAD luciferase reporter assay and functional analyses, we identified CT-707, a China-FDA approved multi-kinase inhibitor under clinical trial with remarkable inhibitory activity against YAP function. CT-707 exhibited prominent cytotoxicity under hypoxia on HCC cells, which was attributable to the inhibition of YAP signaling.

AKR1C1 Activates STAT3 to Promote the Metastasis of Non-Small Cell Lung Cancer.

Metastasis is the leading cause of mortality for human non-small cell lung cancer (NSCLC). However, it is difficult to target tumor metastasis because the molecular mechanisms underlying NSCLC invasion and migration remain unclear. GEO data analyses and IHC analyses were performed to identify that the expression level of AKR1C1, a member of human aldo-keto reductase family, was highly elevated in patients with metastasis or metastatic foci of NSCLC patients.

Polysarcosine brush stabilized gold nanorods for in vivo near-infrared photothermal tumor therapy.

Unlabelled: Gold nanorods (AuNRs) are suitable candidates for photothermal therapy in vivo, because of their excellent ability to transfer near-infrared (NIR) light into heat. However, appropriate surface should be generated on AuNRs before their in vivo application because of the low colloidal stability in complicate biological environment and relatively strong toxicity compared to their pristine stabilizer cetyltrimethylammonium bromide. In the current study, polysarcosine (PS), a non-ionic hydrophilic polypeptoid whose structure is similar to polypeptides, bearing repeating units of natural α-amino acid, was used to stabilize AuNRs due to its excellent hydrophilicity and biocompatibility.

CT-707, a Novel FAK Inhibitor, Synergizes with Cabozantinib to Suppress Hepatocellular Carcinoma by Blocking Cabozantinib-Induced FAK Activation.

Hepatocellular carcinoma is among the leading causes of cancer-related deaths worldwide, and the development of new treatment regimens is urgently needed to improve therapeutic approach. In our study, we found that the combination of a Met inhibitor, cabozantinib, and a novel FAK inhibitor, CT-707, exerted synergistic antitumor effects against hepatocellular carcinoma in vitro and in vivo Interestingly, further studies showed that therapeutic concentrations of cabozantinib increased the phosphorylation of FAK, which might attenuate the antitumor activity of cabozantinib. The simultaneous exposure to CT-707 effectively inhibited the activation of FAK that was induced by cabozantinib, which contributes to the synergistic effect of the combination.