Despite the breakdown of the blood-brain barrier in brain metastases of breast cancer, traditional chemotherapy does not typically accumulate at sufficient concentrations to induce cytotoxicity. Here, Mittapalli and colleagues have designed a nanoconjugate of hyaluronic acid and paclitaxel that is small enough to passively get through the leaky tumor vasculature and to enter into the tumor interstitial space. Once there, the hyaluronic polymers promote CD44 receptor-mediated internalization of the nanoconjugate. Once the nanoconjugate is taken up into the cell, paclitaxel remains cytotoxic. This nanoconjugate system reduced lesion burden in the brain and improved overall survival in a preclinical model of brain metastases of breast cancer.Members of conventional drug classes targeting the MET pathway have faced multiple challenges, including specificity, selectivity, partial agonism, and HGF-dependent activity. Olwill and colleagues discovered and characterized for the first time a novel MET inhibitor (PRS-110) based on a new class of biopharmaceuticals called Anticalins. The monovalent binding nature of Anticalins makes them exquisitely suited for the antagonism of receptor tyrosine kinases, unlike bivalent mAbs, which can lead to receptor activation. The manuscript demonstrates the drug-like properties of this novel inhibitor, which supports its evaluation in a future clinical trial.Synthetic cannabinoids (CB), such as WIN 55,212-2, inhibit the growth of solid tumors and mechanisms can be CB receptor-dependent or -independent. Sreevalson and Safe showed that WIN 55,212-2 inhibited colon cancer cell growth and survival, and an important underlying pathway for these responses was due to downregulation of the specificity protein (Sp) transcription factors Sp1, Sp3, Sp4, and Sp-regulated genes. The mechanism was CB receptor-independent and due to induction of protein phosphatase 2A-mediated disruption of miR-27a-ZBTB10 (an Sp repressor). The design of future applications of WIN 55,212-2 for individual or combined chemotherapies can now be guided by these novel mechanistic insights.MicroRNA-141 (miR-141) was shown to play an important role in tumorigenesis. However, the exact role of miR-141 in pancreatic cancer has not yet been elucidated. In the present study, Zhao and colleagues discovered that downregulation of miR-141 in pancreatic cancer was correlated with poor overall survival and MAP4K4 was the direct target of miR-141. Restoration of miR-141 increased the chemosensitivity in vitro. Moreover, overexpression of miR-141 or knockdown of MAP4K4 inhibited the tumor growth of mice xenografts in vivo. All these findings suggest that miR-141 targets MAP4K4 and acts as a tumor suppressor in pancreatic cancer cells.