Why is it so hard to cure cancer?

 Why is it so difficult to cure cancer? We've harnessed electricity, sequenced the human genome, and eradicated small pox. But after billions of dollars in research, we haven't found a solution for a disease that affects more than 14 million people and their families at any given time. 

Cancer arises as normal cells accumulate mutations. Most of the time, cells can detect mutations or DNA damage and either fix them or self destruct. However, some mutations allow cancerous cells to grow unchecked and invade nearby tissues, or even metastasize to distant organs. Cancers become almost incurable once they metastasize. And cancer is incredibly complex. It's not just one disease. There are more than 100 different types and we don't have a magic bullet that can cure all of them. For most cancers, treatments usually include a combination of surgery to remove tumors and radiation and chemotherapy to kill any cancerous cells left behind. Hormone therapies, immunotherapy, and targeted treatments tailored for a specific type of cancer are sometimes used, too. In many cases, these treatments are effective and the patient becomes cancer-free. 

But they're very far from 100% effective So what would we have to do to find cures for all the different forms of cancer? We're beginning to understand a few of the problems scientists would have to solve. First of all, we need new, better ways of studying cancer. Most cancer treatments are developed using cell lines grown in labs from cultures of human tumors. These cultured cells have given us critical insights about cancer genetics and biology, but they lack much of the complexity of a tumor in an actual living organism. It's frequently the case that new drugs, which work on these lab-grown cells, will fail in clinical trials with real patients. One of the complexities of aggressive tumors is that they can have multiple populations of slightly different cancerous cells. Over time, distinct genetic mutations accumulate in cells in different parts of the tumor, giving rise to unique subclones. For example, aggressive brain tumors called glioblastomas can have as many as six different subclones in a single patient. This is called clonal heterogeneity, and it makes treatment difficult because a drug that works on one subclone may have no effect on another. 

Here's another challenge. A tumor is a dynamic interconnected ecosystem where cancer cells constantly communicate with each other and with healthy cells nearby. They can induce normal cells to form blood vessels that feed the tumor and remove waste products. They can also interact with the immune system to actually suppress its function, keeping it from recognizing or destroying the cancer. If we could learn how to shut down these lines of communication, we'd have a better shot at vanquishing a tumor permanently. Additionally, mounting evidence suggests we'll need to figure out how to eradicate cancer stem cells. These are rare but seem to have special properties that make them resistant to chemotherapy and radiation. In theory, even if the rest of the tumor shrinks beyond detection during treatment, a single residual cancer stem cell could seed the growth of a new tumor. Figuring out how to target these stubborn cells might help prevent cancers from coming back. Even if we solved those problems, we might face new ones. Cancer cells are masters of adaptation, adjusting their molecular and cellular characteristics to survive under stress. When they're bombarded by radiation or chemotherapy, some cancer cells can effectively switch on protective shields against whatever's attacking them by changing their gene expression. Malignant cancers are complex systems that constantly evolve and adapt. To defeat them, we need to find experimental systems that match their complexity, and monitoring and treatment options that can adjust as the cancer changes. 

But the good news is we're making progress. Even with all we don't know, the average mortality rate for most kinds of cancer has dropped significantly since the 1970s and is still falling. We're learning more every day, and each new piece of information gives us one more tool to add to our arsenal.