A phase Ib dose escalation study of oral monotherapy with KX2-391 in elderly patients with acute myeloid leukemia.

Poor tolerance to standard therapies and multi-drug resistance complicate treatment of elderly patients with acute myeloid leukemia (AML). It is therefore imperative to explore novel tolerable agents and target alternative pathways. KX2-391 is an oral non-ATP-competitive inhibitor of Src kinase and tubulin polymerization.

A Primary Care Provider's Guide to Clinical Needs of Women With Spinal Cord Injury.

Women are a growing proportion of individuals with SCI and have distinctive health needs spanning the life course that demand deliberate consideration and clinical expertise. Practitioners caring for women with SCI must incorporate broad medical knowledge of SCI physiology and health promotion for women, including differences in complication rates following SCI, and work collaboratively with rehabilitation, medical, and surgical specialists to optimize function and health for women with SCI. Clinical researchers must continue to perform population-based studies to best characterize the evolving needs of women with SCI and evaluate treatment efficacy and care delivery models to best serve this population.

Targeting Notch enhances the efficacy of ERK inhibitors in BRAF-V600E melanoma.

The discovery of activating BRAF mutations in approximately 50% of melanomas has led to the development of MAPK pathway inhibitors, which have transformed melanoma therapy. However, not all BRAF-V600E melanomas respond to MAPK inhibition. Therefore, it is important to understand why tumors with the same oncogenic driver have variable responses to MAPK inhibitors.

BRAF Inhibition Stimulates Melanoma-Associated Macrophages to Drive Tumor Growth.

Purpose: To investigate the roles of melanoma-associated macrophages in melanoma resistance to BRAF inhibitors (BRAFi).

Experimental Design: An in vitro macrophage and melanoma cell coculture system was used to investigate whether macrophages play a role in melanoma resistance to BRAFi. The effects of macrophages in tumor resistance were examined by proliferation assay, cell death assay, and Western blot analyses.

The novel SMAC mimetic birinapant exhibits potent activity against human melanoma cells.

Purpose: Inhibitor of apoptosis proteins (IAP) promote cancer cell survival and confer resistance to therapy. We report on the ability of second mitochondria-derived activator of caspases mimetic, birinapant, which acts as antagonist to cIAP1 and cIAP2, to restore the sensitivity to apoptotic stimuli such as TNF-α in melanomas.

Experimental Design: Seventeen melanoma cell lines, representing five major genetic subgroups of cutaneous melanoma, were treated with birinapant as a single agent or in combination with TNF-α.

PLX4032, a potent inhibitor of the B-Raf V600E oncogene, selectively inhibits V600E-positive melanomas.

Targeted intervention of the B-Raf V600E gene product that is prominent in melanoma has been met with modest success. Here, we characterize the pharmacological properties of PLX4032, a next-generation inhibitor with exquisite specificity against the V600E oncogene and striking anti-melanoma activity. PLX4032 induces potent cell cycle arrest, inhibits proliferation, and initiates apoptosis exclusively in V600E-positive cells in a variety of in vitro experimental systems; follow-up xenograft studies demonstrate extreme selectivity and efficacy against melanoma tumors bearing the V600E oncoproduct.