[gdpawel]

Endothelial growth factor (EGF) is an important activator of angiogenesis. EGF causes endothelial cells to grow. Research has shown that oncogenes (genes that help cancer cells grow), cytokines (substances produced by the immune system), and hypoxia (a low-oxygen environment, which is common in tissues around solid tumors) can all directly or indirectly activate EGF, thereby starting angiogenesis.

EGF causes angiogenesis by attaching to special receptors (proteins on the outside of cancer cells that act like doorways), and this action starts a series of chemical reactions inside the cell. Because EGF is so important to angiogenesis, it is a target of new cancer treatments. For example, the drug bevacizumab (Avastin) blocks a receptor for EGF.

In addition to EGF, researchers have identified a dozen other activators of angiogenesis, some of which are similar to EGF, VEGF being one of them. Endostatin is a protein that talc stimulates healthy cells to produce after placed into the chest cavity during thoracoscopy, to inhibit the growth of tumors by cutting the flow of blood to metastatic lung tumors.

Avastin can be tested with a EGFR biomarker assay because the "target" of Avastin is not the cells themselves, but rather the hormone (VEGF) secreted by the tumor cells. Avastin complexes with free VEGF and blocks its action.

At a critical point in the growth of a tumor, the tumor sends out signals to the nearby endothelial cells to activate new blood vessel growth. Two endothelial growth factors, VEGF and basic fibroblast growth factor (bFGF), are expressed by many tumors and seem to be important in sustaining tumor growth.

Avastin is a monoclonal antibody, a type of genetically engineered protein. Monoclonal antibodies are substances made in the laboratory that recognize and then attach to specific proteins on the outside of cancer cells. They may be used to stimulate the immune system to attack cancer cells or to deliver radiation, chemotherapy, or other biologic therapies more directly to a tumor.

Avastin directly binds to the protein VEGF, which spurs the growth of blood vessels. Angiogenesis is dependent on VEGF. Avastin directly binds to VEGF to directly inhibit angiogenesis (microvasculature regression). Within 24 hours of VEGF inhibition, endothelial cells have been shown to shrivel, retract, fragment and die by apoptosis. VEGF can cut off the supply of vessels that spring up to feed a tumor, but there is some uncertainty how Avastin works, or if it can get "inside" a cell.

And here's another possible indication. Scientists from the University of Innsbruck, Austria determined (via immunohistochemical staining for VEGF) that patients with Carcinomatous Meningitis (Leptomeningeal Carcinomatous) from breast cancer, significant amounts of VEGF are released into the cerebrospinal fluid (CSF). VEGF in CSF may be a useful biologic marker not only for the diagnosis but also the evaluation of treatment response in Carcinomatous Meningitis.

With respect to the metastasis, it is literally a cancer that has moved. It may have mutated further (cancer is itself a mutation that occurs within a cell that was intended to look and function as a normal cell but somewhere along the line the genetic "wiring" got crossed and instead of simply dying as it should have done, it divided and produced offspring cells that shared the same mutation as the original parent cell) in some respects - often it becomes more resistant to therapy than the primary (original) tumor - but fundamentally, it remains the same tumor-type.

In other words, a rectal cancer in the lung remains rectal cancer. The cell has identifiable characteristics which usually allow the pathologist to determine its point of origin. In fact, sometimes in cancer, a primary tumor never is located but the metastatic cells can be identified as having come from a specific organ system because of the way they look and because they express certain molecules which can be identified chemically.

Therefore, the treatment for a breast cancer, for example, that has metastasized to a different part of the body generally is treated in a similar manner as if the tumor cells all were contained within the region of the breast.

However, from the viewpoint of assay-directed therapy, none of that matters because it doesn't necessarily treat all breast cancers with "the" breast cancer protocol or all rectal cancers with "the" rectal cancer protocol (even if there were only one - in fact, there are several protocols to choose from).

Instead, the whole point of functional tumor cell profiling is to determine, individually - that is, for each patient - precisely which drug or drugs is best able to kill that patient's own cancer cells - no matter which drug that happens to be and no matter what type of cancer it is.

If you visit the National Cancer Institute website, you'll see that for virtually all cancers, there is no single "best" regimen listed. Instead, you'll find that, for each cancer type, many drugs and drug combinations have been proven in clinical trails to produce about the same result among large groups of unselected patients.

However, looking at the individual patients within a clinical trial, all of whom have the same type and stage of cancer, some patients do not respond at all to a specific treatment while others respond very well and, even in some of the very difficult cancer types, some patients achieve long-term remissions and even cures.

What this suggests is, considering that there are many drug regimens which are equally-accepted by the NCI and by oncologists, these drugs regimens should not be administered blindly but rather each patient's cancer cells should be tested to determine which of the otherwise equally-acceptable drug regimen has the very best chance of benefiting that particular patient.