Unfortunately, one of the most common ways we interact with cell biology as part of our daily experiences is cancer. Shown here is a picture of pancreatic cancer cells. It is very likely that everyone participating in this specialization knows someone with cancer, someone who is in remission, or someone who has died of cancer, or you've had cancer yourself. This includes myself, watching my in-laws die of cancer within six months of one another was a terrible experience. We're also taught to watch out for signs of cancer and to get regular check-up and tests to prevent cancer. For example, maybe you've seen marketing about wearing sunscreen and about how to watch from mole or skin changes that could be indicative of skin cancer. Maybe you do breast or testicular self-exam to check for presence of unusual lumps or bumps. Maybe part of your health care routine is that you get a colonoscopy every year, which looks for abnormalities in your intestines, or maybe you get a pap smear which I mentioned earlier in this module which looks at the cells on the cervix to check for signs of cervical cancer. Preventing cancer is a big reason why we go to the doctor for annual checkups. Since cancer impacts so many people, it's not uncommon to see various fundraisers for different kinds of cancer as well to support cancer research or cancer patients or families of patients who have cancer. Biologically, what is cancer? What does it have to do with our cells? I like using the analogy of cancer as rogue cells. They're cells that aren't doing what they're supposed to be doing. Normally, cells work together for the good of the body. Cells talk to one another to say when to divide, when to grow, and when to die. It's like a beehive where all the individuals are working together for the good of the group. Rogue cells are the ones who stop listening and they do whatever they want to do. So they divide when they're not supposed to for example, or they don't die when they're supposed to die. Cells have checkpoints or fail-safes someplace in order to prevent this from happening. But sometimes the fail-safes fail too. Getting cancer is a lot like an airplane crash. There are many, many fail-safes to prevent both. They're both relatively rare as well and many things have to go wrong for either to occur. In terms of cancer, a fail-safe could be lost because of DNA mutations. As I've mentioned before, a DNA is the instruction book of the cells. When mutations occur, those instructions can change. Think of it like having a piece of paper with notes on it and you spill some water or coffee on it and you dry it off and you look at it. Sometimes you can still read the paper and sometimes you can't, it's obscure. So damaging mutations mittle the instructions for building proteins, because remember, DNA contains instructions for building proteins and the proteins actually do the work in our cells. Well, if you can't read the instructions or you read them wrong and it's a protein whose job is to prevent you from getting cancer, well now we're not building and folding it correctly and now it's no longer doing its job either, increasing the likelihood of getting cancer. So how do DNA mutations occur? There's a lot of ways. So for example, ultraviolet radiation from the sun or UV rays, they can be exposed to carcinogens. Carcinogens are chemicals that specifically cause cancer. We experience those as part of our environment or sometimes in our food. Now, DNA mutations are a normal biological process and it's a very important biological process as well. It's not all bad. Mutations help to generate genetic diversity. We need that because it means that we're more likely to survive and it also facilitates evolution. That's something we'll come back to in course three. Overtime, we've evolved ways of dealing with DNA mutations. So particularly ways to be able to correct bad DNA mutations. So there's proteins, and so remember proteins like the workers in the cell and one job of a certain group of proteins is to proofread and correct DNA damage and fix these mutations. Others are designed to stop the cell cycle and say, "Hey, we're not going to divide anymore. I found errors and this cell needs to go through apoptosis or programmed cell death." A gene that you may be familiar with that encodes one of these DNA repair proteins is called BRCA1, which is associated with breast cancer. We all have BRCA genes. But if we inherit a bad copy of a BRCA gene that leads to a defective protein that's not as good at fixing damaged DNA, well, then they're more likely to develop breast cancer. Another way of getting cancer that we don't usually think about is from viruses. Some viruses like the human papillomavirus or HPV, are associated with cancer. These viruses infect cells and change the behavior which can lead to cancer. For example, HPV is associated with both cervical and throat cancer. Now that we've talked about how cells go rogue, how does a single cell or a group of cells then lead to cancer? We try to prevent cancer by catching these rogue cells before they start to spread or metastasize. For example, if you've had a mole removed, if it looks precancerous, your doctor will likely call you to come in and have the margins removed to make sure that all the rogue cells are removed as well. Once cancer begins to spread it becomes more serious. That's why it's so important to get those margins, get all those cells before they start to spread anywhere else. But when someone has cancer that spreads in their body, that does not mean there are multiple kinds of cancer. For example, someone who has breast cancer that spreads into the lungs and the brain does not have breast, lung, and brain cancer. They have breast cancer that has spread throughout their body. One of the reasons why melanoma or skin cancer is so dangerous is because in order to spread, the cancer needs to break through the basement membrane of our skin. The basement membrane is really tough. It's designed to protect our bodies. This is why a mole spreading is an early warning sign, it's unable to go down. It hits that basement membrane and it stops, but it's still growing, so it needs to grow somewhere. It starts to grow up, so a mole may become raised or outward, a mole may begin to spread. Cells that are really aggressive and can get through that final safe, that basement membrane, then it's really easy for them to invade the rest of the body if they can make it past that barrier. Good news about skin cancer is it is completely curable if you catch it in time before it starts to spread. You got to get those rogue cells out before they break through the basement membrane and go in to cause additional troubles. There are two groups of proteins involved in preventing cells from going rogue, tumor suppressors and proto-oncogenes. I mentioned one example of a tumor suppressor already, brca. Tumor suppressors work to prevent cancer. So a tumor suppressor, it's something that's preventing you from getting a tumor. Another example of a tumor suppressor that you may be familiar with is called p53. P53 is also called the guardian of the genome, and it works to prevent cancer both by stopping the production of new cells and by promoting cell depth. In fact, the loss of p53 is very common in cancerous tissues. Another example of a tumor suppressor is APC. Mutations in APC are associated with developing colon cancer. Proto-oncogenes are the opposite of tumor suppressors. We need cells to divide, that's a normal process. For example, if you get a paper cut in your skin, we need to produce more cells to heal that wound. Your hair is growing because cells are dividing at the root of your hair. Children are growing taller. But where do these new cells come from, and how did these cells know to divide? Proto-oncogenes in our normal body are telling cells, "Okay, you can divide." So they're very tightly controlled when they can say, "Okay, you're okay to divide." But when proto-oncogenes are mutated, they become what are called oncogenes. Now a cell is beginning to divide in an out-of-control manner, which can lead to cancer. Think of it like driving a car. Proto-oncogenes give a little bit of gas so the car can go a little bit. An oncogene means you've lost control, you are flooring it, you're going way too fast and you're speeding out of control. So these cells are growing way too fast now. Our genes are really important for understanding the hows and whys of getting cancer, but it's more than just Star genetics. One of the most important things to remember about how and why cells go rogue, and one thing that we're still really trying to understand is that it's not just our genetics, but it's also an environment as well, and how our genetics and our environment are interacting to determine if we get cancer or we don't get cancer at all. Having certain gene variants of tumor suppressors like brca only increases your chances of getting breast cancer. It doesn't guarantee that you will. Just like if you have normal copies of brca, that doesn't mean you will never develop breast cancer. The environment is really important for understanding who does and does not get breast cancer. Our genetic background and how it interacts with our environment is really going to dictate who gets cancer. This is a major research question right now in Oncology and cancer Biology. We're all aware of some risk factors that come in from our environment. For example, cigarette smoke contains about 69 different cancer-causing chemicals or carcinogens Asbestos was used as insulation in buildings or as part of textured paint until the 1970s. It's no longer used as now we know it's a carcinogen. Then there are compounds like formaldehyde, which is used to preserve animals specimens, and it's also a natural by-product of our metabolism as well. Relating this back to course one and our discussion of natural and synthetic compounds, formaldehyde and asbestos are both naturally occurring. One of the reasons to finding a cure for cancer is so difficult, is because there's many different interacting processes, those fail-safes that I mentioned, and they all have to go wrong. It's hard to understand the various fail-safes that are all interacting with one another and exactly how and why they fail. Many different genes are also interacting with one another, and these interactions are impacted by environmental factors as well. One of the exciting parts about Biology and sciences is that we're constantly learning new things, including how cancer works. With a better understanding of how cancer works, new treatments will follow next.