As a grad student I subscribe to several science journals’ mailing lists. Each time a new issue is published I receive an email giving me a list of the table of contents for that issue. Most of the journals I subscribe to are HIV or virus and pathogen based, but I do get Nature and Science so I can see what’s going on in other fields. There’s some pretty cool stuff being done spanning a lot of disciplines so I find that on Wednesdays and Thursdays (because most of the journals publish these days for some reason) I spend a lot of my “away from the bench” time reading science news. This is going to get worse because I recently joined twitter and have started following Science and Nature, Natural Geographic and WHO (and local traffic!).
There was this really cool article in Science recently about a new cancer drug that can “cure” multiple types of cancer (The CD47-signal regulatory protein alpha (SIRPα) interaction is a therapeutic target for human solid tumors. Willingham et al. PNAS 2010 www.pnas.org/cgi/doi/10.1073/pnas.1121623109. To appreciate how amazing this is, you first need to appreciate how complex cancer is. There are many factors that make cancer treatment complicated. The first is the variety of cancers that are present – liver, lung, bone, blood, to name a few. Each cancer affects a different part of the body, which means that different types of cells are involved, which is why you typically need different treatment plans for different types of cancer. So, you’ve started with one disease that has different types – if that wasn’t complicated enough to treat, each cancer is different, just like each person is different. Cancer develops when your cells have mutations that prevent them from behaving normally. There are several different tumour suppressor proteins that keep your cells from growing uncontrollably, which is a hallmark of cancer. Think of when you have a cut that has healed – new skin cells grow to cover the cut, then when the cut is healed no more new skin cells are grown – you don’t need them and your skin cells are programmed to know when you have “enough”. In cancer, the cells don’t know when to stop growing. Since this is very important to prevent, there are multiple “checks” in place. Each tumour that develops in different people, even if it is in the same organ, likely has a different set of mutations that lead to it being able to grow. Different mutations react to treatments in different ways. This is why two patients that both have the same type of cancer (ex. Breast cancer) could have different treatments.
In addition to these problems, cancer cells are usually “invisible” to the immune system. The macrophage cells of the immune system monitor the body for cells that aren’t normal (cells infected with viruses or bacteria, or cancer cells in some cases) and “eat” the unhealthy cells. Cancer cells can “hide” themselves and the immune system doesn’t destroy them. This allows the tumor to grow with no interference.
Several research groups have shown that the expression of a protein called CD47 on the surface of healthy cells interacts with a protein on macrophages called SIRPα, and this give the macrophage a “don’t eat me signal” so the healthy cell survives.
Willingham et al collected ovarian, breast, colon, bladder, glioblastoma, hepatocellular carcinoma and prostate tumor cells from patients. They examined the tumor cells and found that CD47 was expressed on almost all the tumor cells. The tumors expressed CD47 at levels 3.3-fold higher than what is seen on healthy cells. This means that the tumor cells have really high levels of the “don’t eat me” signal, which may be why the immune system hasn’t destroyed the tumor.
I thought there next step of experiments was very interesting. The researchers wanted to see if using an antibody to block CD47 (so it couldn’t interact with SIRPα) would allow the macrophages to eat the tumor cells. A special microscope with a camera is used to watch macrophages eat tumors. They found that if they treated the tumor cells with an antibody against CD47 the macrophages were now able to eat the tumor cells. If they didn’t add the antibody, nothing happened to the tumor cells. The next part was really cool – they created xenograft tumors by taking patient tumors and putting them into immunodeficient mice. Once the tumors were established they treated the mice with the CD47 antibody. Tumor growth was inhibited in these mice, and they had longer survival. In some mice, the tumor was actually eliminated. They repeated these experiments in immunocompetent mice, and the same thing was found.
This study is pretty cool because they show that they can treat and even eradicate different types of cancer in mice, using the same treatment for each cancer. A finding like this could revolutionize cancer treatment. While this study is a sign of hope in the cancer research field, it is only one study. More information about the mechanism of exactly how this works, and more studies will need to be undertaken before clinical trials can begin. But it is definitely a step in the right direction for cancer treatments!
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