Fibulin 3 as a Mesothelioma Marker – Latest Research
The search for a mesothelioma marker has been a long awaited quest. Numerous reasons warrant the search of a clinical marker for the detection of mesothelioma. Despite the current advances in radiotherapy and chemotherapy, the median survival after its diagnosis is 12 months. It is not easy to develop new methods for helping someone with cancer and Mesothelioma in general. This is primarily because Imaging techniques for detection are limited by a low sensitivity and specificity. Furthermore, clinicians tend not to consider it in the differential diagnosis delaying its investigation.
In the current issue of NEJM, Pass HI et al. have shown that a novel serum and effusion marker Fibulin 3 not only has a high sensitivity and specificity for the detection of mesothelioma compared to other investigated markers, but also a higher positive predictive value and is independent of the duration of asbestos exposure.
Fibulin 3 is an extracellular glycoprotein, normally expressed in low quantities and is inversely related to cell growth. However, this study did not address the question as to why Fibulin 3 levels are elevated in mesothelioma, the mechanism by virtue of which it is increased or whether blocking it improves prognosis. Prospective cohort studies enrolling patients with other tumor types and those with benign effusions are required to address these questions.
Phase 2 RCT on a novel Angiotensin Receptor Inhibitor LCZ696
Heart failure with both preserved and deranged ejection fraction is associated with a significant morbidity and mortality. Effective treatments for patients with heart failure and preserved (greater than 45%) ejection fraction have been a long awaited quest. In the current issue of The Lancet, Solmon et al have presented the findings from a double blind RCT on valsartan 160 mg twice daily or LCZ696 at a dose of 200 mg twice daily.
LCZ696 is an angiotensin receptor neprilysin inhibitor (ARNI), which is a combination of valsartan and AHU-377, in a 1:1 mixture. The mechanism of action of AHU-377 is an inhibition of enzyme neprilysin which degrades vasodialtors atrial and brain natriuretic peptide (BNP).
The patients were followed for 12 weeks for the changes in primary end point, which is levels of pro-BNP It was observed that compared to valsartn, the combination drug LCZ969 was associated with a significant reduction in the pro-BNP levels. Adverse effects were similar in the 2 study groups. Whether or not this correlates with clinical parameters such as decreased mortality is yet to be investigated. A large phase 3 RCT is underway to address the limitations of the study.