Elevated Levels of Mutant Circulating Tumor DNA and Circulating Hepatocyte Growth Factor Are Associated With Poor Prognosis in Patients With Metastatic Melanoma.

Purpose: We performed a retrospective exploratory analysis to evaluate the prognostic and predictive effect of two circulating biomarkers, mutant circulating tumor DNA (ctDNA) and circulating hepatocyte growth factor (cHGF), in metastatic melanoma.

Materials And Methods: This study evaluated patients from BRIM-3, a phase III trial comparing vemurafenib and dacarbazine in 675 patients with mutated advanced melanoma. ctDNA was measured using droplet digital polymerase chain reaction, and cHGF was measured by enzyme-linked immunosorbent assay.

Battling Btk Mutants With Noncovalent Inhibitors That Overcome Cys481 and Thr474 Mutations.

The Bruton's tyrosine kinase (Btk) inhibitor ibrutinib has shown impressive clinical efficacy in a range of B-cell malignancies. However, acquired resistance has emerged, and second generation therapies are now being sought. Ibrutinib is a covalent, irreversible inhibitor that modifies Cys481 in the ATP binding site of Btk and renders the enzyme inactive, thereby blocking B-cell receptor signal transduction.

HGF as a circulating biomarker of onartuzumab treatment in patients with advanced solid tumors.

The objective of this study was to evaluate circulating hepatocyte growth factor (cHGF) as a pharmacodynamic biomarker of Met inhibition for onartuzumab (MetMAb, OA5D5v2) in a phase I trial in patients with advanced cancers and a phase II trial in non-small cell lung cancer (NSCLC). The phase I study was a dose escalation trial with onartuzumab administered i.v.

Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors.

Mutationally activated kinases define a clinically validated class of targets for cancer drug therapy. However, the efficacy of kinase inhibitors in patients whose tumours harbour such alleles is invariably limited by innate or acquired drug resistance. The identification of resistance mechanisms has revealed a recurrent theme—the engagement of survival signals redundant to those transduced by the targeted kinase.

Manufacturing of large numbers of patient-specific T cells for adoptive immunotherapy: an approach to improving product safety, composition, and production capacity.

We have developed an innovative system for ex vivo processing of patient-specific cell products to produce large numbers of T-lymphocytes in support of phase 2 adoptive immunotherapy trials for hematologic malignancies. Extensive efforts were undertaken to close the cell processing system to improve the safety profile of the process and comply with new federal regulations regarding cell and tissue processing. Our results demonstrate that apheresis products can be processed in a closed system (Cytomate) with similar yields (approximately 4 x 10(9) mononuclear cells/apheresis) and recoveries (approximately 60% of starting mononuclear cells) to manual cell processing.