NCI Ras Initiative: Let’s get together and drug RAS!

Non-scientist friends and relatives often ask me whether I am “curing” cancer, and question why the cure for cancer doesn’t already exist following decades of funding for research. Worse, some social media conspiracy theorists are irrevocably convinced that the cure for cancer already exists, but, for monetary gain, the government only allows companies to treat patients with subpar chemotherapeutics that will only  prolong the disease, not cure it. When faced with such conversations, which are usually a testament to the poor public science education in this country, I tell people about the complex nature of cancer and the difficulty of cancer drug development. I try to explain that cancer is different in every person. I discuss the heterogeneous nature of tumors, and how different sections of a single tumor are genetically distinct from one another. I explain that it is incredibly difficult to identify a therapeutic window where a compound can selectively target and kill tumor cells and not healthy cells, because tumor cells are just corrupted versions of your own healthy cells. I even quote my graduate research mentor, Dr. Channing J. Der and say, “Cancer drug design is not for the faint of heart.” Then, I usually tell people the story of the RAS proteins.

 Over thirty years ago, the RAS proteins were implicated as oncogenes, which are genes that have the potential to lead to cancer when not properly regulated. Today, we know that activating mutations in the three RAS isoforms, N-RAS, H-RAS, and K-RAS, are present in nearly one-third of all human cancers. Additionally, these mutations actively drive some of the most aggressive and deadly tumor types, including lung, colon, skin, and pancreatic cancer. These discoveries sparked decades of unfruitful efforts to design inhibitors of RAS as a means to selectively target and eliminate tumor cells that are dependent upon RAS signaling for growth and survival, while avoiding damage to normal cells. After three decades, and an unthinkable amount of money and effort, no pharmaceutical company or academic institution has been successful in targeting RAS proteins with any clinical efficacy.

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