Mesothelioma Prognosis and Placenta Growth Factor

Mesothelioma, like other cancers, grows and spreads through a process of angiogenesis, the growth of new blood vessels.  Without a blood supply a mesothelioma tumor would starve and die.  Vascular endothelial growth factor (VEGF) is a protein made by cells that stimulates new blood vessel formation.  Therefore, treatments that slow or stop VEGF in tumors can slow or stop the formation of blood vessels (“anti-angiogenesis”) and thereby halt the growth and spread of cancer.

One type of VEGF is placenta growth factor (P1GF).  A recent study investigated whether P1GF is over expressed in mesothelioma.¹   If it is this could present a new therapeutic target.  Specimens from twenty-seven patients with mesothelioma were compared with specimens from ten healthy patients.  The researchers found that P1GF was not expressed in the normal mesothelium of the healthy subjects.  However, it was over expressed in eleven (41%) of the patients with mesothelioma.

In this study, the mean survival of the mesothelioma patients after extrapleural pneumonectomy (EPP) was 17 months, but the patients with the least P1GF expression survived the longest.  In fact, no relationship was found between tumor stage and survival or between tumor stage and PIGF expression.  This would suggest that P1GF plays a “pivotal role” in the recurrence and progression of mesothelioma after EPP.

There are many anti-VEGF therapies being tested in other cancers such as bevacizumab (Avastin), ranibizumab (Lucentis), sunitinib (Sutent), sorafenib (Nexavar), axitinib, and pazopanib.  However, according to a study published in 2008 while anti-VEGF drugs can show therapeutic efficacy in animals and in some human cancers, “the benefits are at best transitory and are followed by a restoration of tumour growth and progression.”²   Nonetheless, more recent studies suggest that P1GF is a promising target and may help alleviate therapeutic resistance for treatments that focus only on VEGF.³   In fact, in one recent study, “the administration of an anti-PlGF antibody was found to cause a significant reduction of malignant mesothelioma cell survival.”⁴

Although the science is just now developing, the understanding of the role of P1GF in mesothelioma and its potential therapeutic targeting holds promise for mesothelioma sufferers.

Endnotes:

1. Pompeo E, et al., Placenta growth factor expression has prognostic value in malignant pleural mesothelioma. Ann Thorac Surg. 2009 Aug;88(2):426-31.

2. Bergers and Hanahan, Modes of resistance to anti-angiogenic therapy. Nature Reviews Cancer 8, 592-603 (August 2008).

3. Loges S, et al., “Antimyeloangiogenic” therapy for cancer by inhibiting PlGF. Clin Cancer Res. 2009 Jun 1;15(11):3648-53. Epub 2009 May 26.

4. Albonici L, et al., Placenta growth factor is a survival factor for human malignant mesothelioma cells.  Int J Immunopathol Pharmacol. 2009 Apr-Jun;22(2):389-401.