We describe the results of a trial in which major antitumor responses were seen in patients with advanced mesothelioma who received the anti-mesothelin immunotoxin SS1P, together with pentostatin and cyclophosphamide, to deplete T and B cells. Of 10 patients with chemotherapy-refractory mesothelioma, 3 have had major tumor regressions with 2 ongoing at 15 months, and 2 others responded to chemotherapy after discontinuing immunotoxin therapy. Antibody formation was markedly delayed, allowing more SS1P cycles to be given, but this alone does not appear to account for the marked antitumor activity observed.
Mesothelioma is a form of lung cancer strongly associated with exposure to asbestos. Even though asbestos has been banned or heavily regulated in most developed nations, due to delayed onset, the number of mesothelioma cases is predicted to climb until around 2020. In the UK, which has the highest mesothelioma incidence worldwide, two new clinical trials are aiming to find treatments for the disease. The Meso2 trial will investigate ganetespib, while the COMMAND trial will examine defactinib. Defactinib specifically targets cancer stem cells, which often survive cancer treatment and cause cancer recurrence. The drug may therefore help prevent relapse after first-line therapy.
Monoclonal antibodies to cytotoxic T-lymphocyte antigen 4 (CTLA4) have therapeutic activity in different tumour types. We aimed to investigate the efficacy, safety, and immunological activity of the anti-CTLA4 monoclonal antibody, tremelimumab, in advanced malignant mesothelioma.
Although the effect size was small in our phase 2 trial, tremelimumab seemed to have encouraging clinical activity and an acceptable safety and tolerability profile in previously treated patients with advanced malignant mesothelioma.
Sorafenib is well tolerated in patients with mesothelioma after completion of platinum-containing chemotherapy. Progression-free survival of sorafenib compares favorably with that reported for other targeted agents, and suggests moderate activity in this disease.
“BAP1 is a deubiquitylase that is found associated with multiprotein complexes that regulate key cellular pathways, including the cell cycle, cellular differentiation, cell death, gluconeogenesis and the DNA damage response (DDR). Recent findings indicate that germline BAP1 mutations cause a novel cancer syndrome that is characterized, at least in the affected families that have been studied so far, by the onset at an early age of benign melanocytic skin tumours with mutated BAP1…”