In this section we will cover Neoangiogenesis which is the formation of new blood vessels in cancer. Blood vessels are formed in two ways vasculogenesis and angiogenesis. Vasculogenesis is the formation of brand new blood vessels from stem cells. Stem cells can create daughter cells that can form multiple different types of cells. In this case, a type of blood stem cell can create all of the cell types necessary to form a new blood vessel, and this largely takes place during embryonic development when brand new blood vessels are required. Angiogenesis, on the other hand, is the formation of new blood vessels which use already existing blood vessels as a structure to build off of. Angiogenesis occurs during growth and development just like vasculogenesis but also occurs during wound healing. And the specific type of angiogenesis that occurs during tumor formation is called neoangiogenesis, which we'll talk about in a couple slides. So all of the blood vessels that exist in the cardiovascular system in one person throughout the body are formed by a combination of vasculogenesis and angiogenesis. And just to recall, blood vessels are required to bring oxygen and nutrients to every cell in the body while simultaneously removing cellular waste and carbon dioxide. And this happens at the capillary level. So capillaries are the smallest blood vessels that exist, and they're small enough to fit in between tissues and to reach all of the cells. Arteries carry oxygen and nutrients to the cells. Arteries connect the veins through capillaries and once the payload of oxygen and nutrients is dropped off, the veins then carry away waste and carbon dioxide back to the lungs and heart. Now that we have a basic understanding of blood vessel formation and its purpose, we can talk about why tumors require new blood vessels to be made. As we have discussed, cancer is uncontrolled cell division. Normal cells do not divide all that much. Cancer cells divides constantly, and therefore tumors grow quickly, more quickly than the existing blood supply to keep up with so they quickly outgrow the source of oxygen and nutrients. Therefore, in order to continue growing, cancer cells actually secrete molecules that cause angiogenesis, or the formation of new blood vessels from existing blood vessels. In the context of cancer, this is actually called neoangiogenesis and it is one of that hallmarks of cancer that Doctor Gialani Zerif discussed in the Introduction to Cancer lecture series. Neoangiogensis is driven by hypoxic conditions or hypoxia. Hypoxia is a condition of low levels of oxygen which occurs when a cell is located too far away from a blood vessel. In the diagram on the left you will see a blood vessel and right next to the blood vessels are red cells with high levels of oxygen underwater called normoxic conditions or normal oxygen. Next to the red cells are purple cells which are exposed to less oxygen, and then blue cells that are exposed to even less oxygen. The blue cells are under hypoxic or low oxygen conditions and the blue cells are driving neoangiogenesis. In the middle panel you see that a new vessel has sprouted from the existing blood vessel and there are now more red cells, and the new blood vessel begins to bring oxygen to those cells. In the final panel on the right, the newly formed vessel has brought oxygen levels up to normoxic conditions or all of the cells turning them red. So these panels illustrate the goal of tumor angiogenesis which is to bring oxygen to all of the tumor cells that are rapidly dividing. As you might imagine, neoangiogenesis is an abnormal process. The natural process of angiogenesis is taken over by tumor cells to make blood vessels where there should not be any blood vessels. So neoangiogenesis typically produces poorly made blood vessels with abnormal vascular organization. You can see on the diagram how normal vasculature is highly organized, whereas cancer vasculature is poorly organized. And in the image, you see a real life example of vasculature sprouting into a fast growing tumor. These tumor vessels are often leaky due to poor cellular organization, and this leads to increased routes of entry into the blood supply by tumor cells. So just to reiterate, more neoangiogenesis means more routes for cancer cells to get out of the primary tumor, get in to the blood supply, and metastasize. So the question arises, can we simply stop the process of neoangiogenesis and therefore stop tumors from growing? This has been tried in multiple ways in the clinic but it hasn't been a home run therapy that we're hoping for. The issue is that stopping the neoangiogenesis only seems to stop new blood vessels from forming, but by the time we are able to detect a tumor, the tumor already has an established blood supply that was made by neoangiogenesis. So stopping new blood vessels would not necessarily stop tumors from getting their necessary oxygen and nutrients. However, this strategy is still somewhat effective in a variety of cancers when combined with other forms of chemotherapy. Once such drug, bevacizumab, inhibits the vascular endothelial growth factor A protein. This protein promotes neoangiogenesis, so bevacizumab therefore inhibits neoangiogenesis. This drug is being used to treat at least four different types of cancer in combination with chemotherapy. Other drugs may be made in the future as well. Okay, so now we're done talking about neoangiogenesis. In our next section we're going to wrap up this lecture by talking about the primary tumor micro environment.
