Major Cancer Regressions in Mesothelioma After Treatment with an Anti-Mesothelin Immunotoxin and Immune Suppression

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.


Two New Trials of Mesothelioma Treatments Begin in the UK

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.


Tremelimumab for Patients with Chemotherapy-Resistant Advanced Malignant Mesothelioma: An Open-Label, Single-Arm, Phase 2 Trial

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.


Phase 2 Study of Sorafenib in Malignant Mesothelioma Previously Treated with Platinum-Containing Chemotherapy

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 and cancer

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…”


Avastin-Containing Chemotherapy May Be Safe in Lung Cancer Patients with Brain Metastases

Bevacizumab (Avastin), which is approved for treatment of a number of advanced-stage cancer types, is commonly avoided in patients with brain metastases (cancer that has spread to the brain) because of fear of brain hemorrhages (bleeding in the brain). A retrospective study of 52 patients with advanced non-small cell lung cancer (NSCLC) who had received chemotherapy containing Avastin found no cases of serious bleeding events and no significant differences in survival or treatment side effects between patients with or without brain metastases. Avastin may therefore be a safe treatment option in NSCLC with brain metastases.

Research paper: https://www.jstage.jst.go.jp/article/acrt/20/2/20_47/_pdf


Overexpression of IGF1R and EGFR Genes May Worsen Lung Cancer Prognosis

The roles of the genes IGF1R and EGFR in lung cancer were examined in patients with non-small cell lung cancer (NSCLC) who had their primary tumor surgically removed. Patients whose tumors had increased expression of both IGFR1R and EGFR were more likely to experience recurrence of the cancer after a shorter amount of time and had shorter survival times after surgery. This finding suggests that concurrent overexpression of IGF1R and EGFR is a negative prognosis factor in NSCLC and may indicate patients who are more likely to benefit from novel treatments with IGF1R inhibitors.

Research paper: http://link.springer.com/article/10.1007/s00280-012-2056-y/fulltext.html


Study Suggests Iressa Effective for Elderly Patients with EGFR-Mutant Lung Cancer

A retrospective study in Japan examined 55 patients aged 75 years or over with inoperable non-small cell lung cancer (NSCLC) who had a mutation in the EGFR gene and received gefitinib (Iressa) as first-line therapy. The treatment was generally well tolerated and patients experienced longer periods without cancer progression (median: 13.8 months) and longer overall survival (median: 29.1 months) than commonly reported for similar patients. While studies using control groups will need to confirm that Iressa is indeed more effective than standard chemotherapy or a placebo, these findings suggest that Iressa may be a preferable first-line treatment in elderly patients with advanced EGFR-mutant NSCLC.

Research paper: http://link.springer.com/article/10.1007/s12032-012-0450-2/fulltext.html


Genetic Variation in P53 May Contribute to Lung Cancer Risk

A study of individuals with and without lung cancer in North India found that those carrying a particular version (or “polymorphism”) of a gene for the protein p53 were more likely to have lung cancer, independent of their age or smoking rate. P53 belongs to a class of proteins called “tumor suppressor proteins,” and is involved in DNA repair, regulating cell growth, and inducing cell death in damaged or abnormal cells. The findings suggest that this version of the p53 gene, called Arg72Pro, may contribute to higher susceptibility for lung cancer, at least in the North Indian population.

Research paper: http://online.liebertpub.com/doi/full/10.1089/dna.2012.1792