Phase I Trial and Pharmacokinetic Study of Lexatumumab in Pediatric Patients With Solid Tumors

Abstract

Pediatric patients tolerate 10 mg/kg of lexatumumab administered once every 14 days, the maximum-tolerated dose identified in adults. The drug seems to mediate some clinical activity in pediatric solid tumors and may work with radiation to enhance antitumor effects.

Metformin sensitizes triple-negative breast cancer to proapoptotic TRAIL receptor agonists by suppressing XIAP expression

“…Despite promising preclinical results, TRAIL receptor agonists have failed to demonstrate significant efficacy, either alone or in combination with chemotherapy, in multiple clinical trials in advanced malignancies [3][4][5][6][7][8]. These disappointing results in clinical trials have been attributed to a number of factors, including de novo and/or acquired resistance to TRAIL receptor agonists, inadequate receptor oligomerization on ligand binding, limiting procaspase-8/10 activation, and lack of biomarkers to predict treatment response [1,2].…”

Non-canonical kinase signaling by the death ligand TRAIL in cancer cells: discord in the death receptor family

“…21,22 The promising antitumor activity in preclinical models has spurred early clinical studies with TRAIL receptor agonists in various tumor types. [23][24][25][26] However, as described below, recent preclinical findings indicate pro-survival, proliferation and even metastatic activity of TRAIL, suggesting more caution when applying these TRAIL receptor agonists, particularly as single agents. In this review, we will give an update on the non-canonical (non-apoptotic) signaling activity of the TRAIL pathway in tumor and non-transformed cells.…”

Targeted immunotherapy for pediatric solid tumors

“…45 A phase I clinical trial in pediatric solid tumors including RMS, soft tissue sarcomas, osteosarcoma, Ewing's sarcoma, hepatoblastoma and nephroblastoma was completed (NCT00428272). 46 While some antitumor activity was evident, complete or partial responses were not realized. Considerations for combination and phase II studies are pending.…”