Multitargeting Pt(IV) Derivatives of Cisplatin or Oxaliplatin Inhibit Tumor Growth in Mice without Inducing Neuropathic Pain.

Cisplatin and oxaliplatin are Pt(II) anticancer agents that are used to treat several cancers, usually in combination with other drugs. Their efficacy is diminished by dose-limiting peripheral neuropathy (PN) that affects ∼70% of patients. PN is caused by selective accumulation of the platinum drugs in the dorsal root ganglia (DRG), which overexpress transporters for cisplatin and oxaliplatin.

EZH2 modulates mRNA splicing and exerts part of its oncogenic function through repression of splicing factors in CML.

The polycomb protein EZH2 is up-regulated in Chronic Myeloid Leukaemia (CML) and associated with transcriptional reprogramming. Here we tested whether EZH2 might also act as a modulator of the mRNA splicing landscape to elicit its oncogenic function in CML. We treated CML cell lines with EZH2 inhibitors and detected differential splicing of several hundreds of events, potentially caused by the transcriptional regulation of splicing factors.

Acute Promyelocytic Leukemia Asian Consortium study of arsenic trioxide in newly-diagnosed patients: impact and outcome.

The Acute Promyelocytic Leukemia Asian Consortium analyzed a contemporaneous cohort of newly-diagnosed APL patients treated with and without frontline arsenic trioxide (ATO) in six centers. The objectives were to define the impact of ATO on early deaths and relapses, and its optimal positioning in the overall treatment strategy. In a 21.

ADAR1-regulated cytoplasmic dsRNA-sensing pathway is a novel mechanism of lenalidomide resistance in multiple myeloma.

Immunomodulatory agents (IMiDs) are a major class of drugs for treating multiple myeloma (MM); however, acquired resistance to IMiDs remains a significant clinical challenge. While alterations in cereblon (CRBN) and its pathway are known to contribute to IMiD resistance, they account for only 20-30% of cases, and the underlying mechanisms in the majority of the resistance cases remain unclear. Here, we identified ADAR1 as a novel driver of lenalidomide resistance in MM.