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Angiogenesis means growth of new blood vessels. As they get bigger, cancers need to grow their own blood vessels. Without its own blood supply, a cancer cannot continue to grow. Two of the most important chemicals controlling blood vessel growth are called vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF-2).
People with mesothelioma have much higher levels of VEGF than people with any other type of cancer. If the VEGF can be blocked, this could control the growth of blood vessels supplying the mesothelioma tumours. This treatment is a type of biological therapy.
With cancer, it's all about the body's bounty of blood. If all the blood vessels in the body were lined up end-to-end, they would form a line that could circle the earth twice. Yet the body produces still more blood vessels on demand, such as to heal wounds or grow embryos. This task of forming new blood vessels -a process called angiogenesis - is also critical to the development of cancer.
In order for a rapidly growing tumor to maintain its growth, a tumor "signals" already existing blood vessels to sprout new branches to feed it - and new tiny vessels develop in short bursts. Given the thousands of miles of blood flow already in place in a human body, vessels usually don't have far to grow to hook up to a tiny tumor that cries for blood. But scientists know that unless a tumor connects to a supply of blood, it will grow to a mere 1,000 cells and then stop. Separating cancer from its blood supply - or keeping them from linking in the first place - is the goal of clinicians and researchers.
Antiangiogenesis therapy drugs:
Bevacizumab has been studied in a number of cancers, including mesothelioma, and bowel, kidney, breast, ovarian, non-small-cell lung, and prostate cancers. One trial recently reported that this drug may increase survival for patients with lung cancer. An American phase 2 trial is testing bevacizumab for mesothelioma, in combination with the chemotherapy drugs gemcitabine and cisplatin.
Another type of antiangiogenesis drug that is been tried for mesothelioma is thalidomide. Despite having such a bad name, it is only dangerous if taken in pregnancy. Thalidomide has been shown to slow the growth of mesothelioma cells. Recently a phase 2 trial has begun throughout Europe using thalidomide for mesothelioma patients.
Further trials looking at this drug used alone or in combination with other treatments are needed so as to find out exactly how effective it is and the best doses to use. There is no current trial in the UK looking at thalidomide, but if you are interested in this type of treatment, talk to your doctor. It may be possible for it to be prescribed for you.
Tumor growth is highly dependent on angiogenesis. Development of veins from tumor angiogenesis as well as tumor-derived lymphatics provide channels through which cancer cells can metastasize. Therefore, antiangiogenesis treatment could represent an effective therapeutic strategy with which to suppress both primary tumor growth and tumor metastasis. Tumor growth can be inhibited by blocking tumor-derived angiogenic signals, or by directly targeting the tumor vascular endothelial cells.
Since the vasculature of tumor tissue is different from normal vasculature, it is possible to develop therapeutic agents that specifically target tumor vasculature. There are also other features that make tumor blood vessels an attractive target compared with tumor cells.
(1) A single vessel supports the survival of many tumor cells by providing of oxygen and nutrients, as well as providing a main route for metastatic spread. Thus, destroying one vascular endothelial cell in vessels of tumor tissue may result in the death of many more tumor cells.
(2) Endothelial cells in the tumor vasculature have a lower mutation rate compared with tumor cells, which means that endothelial cells will be unlikely to acquire resistance to the therapeutic drugs.
(3) Angiogenesis is infrequent in the adult, which means that therapies which target angiogenic endothelial cells in tumor vasculature may not damage normal endothelial cells and therefore may have minimal toxicities.
(4) Tumor vascular targeting therapy as well as antiangiogenesis therapy could control tumor growth independently of tumor-cell type. In other words, one vascular targeting agent may be effective in many tumor types.
(5) The endothelial cells are easily accessible by intravenously administrated therapeutic agents, thus circumventing the formidable problem of transcytosis across the vascular wall and diffusion throughout tumor tissue.
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