Metastasis is the process by which cancer cells disseminate from one part of the body to another. When we talk about cancer as a fatal disease, it is really metastasis we are discussing: it is responsible for over 90% of cancer deaths. Decades of investigation have revealed startling details into how cancers form and what molecular changes promote metastasis. Despite this, almost no attention has been paid to the ultimate consequence of cancer, which is how do metastatic cancer cells kill the host?
The vast majority of cancer treatments aim to kill cancer cells. Chemotherapies act to simply kill cancer cells faster than normal cells. More modern "targeted" therapies aim to kill cancer cells due to specific genetic vulnerabilities. In all cases, these approaches are thwarted by resistance to the drugs, likely because we try to kill billions of cells which are incredibly adaptable and aim for their own survival. This study is aimed squarely at patients with metastatic cancer. Our initial studies will focus upon metastatic melanoma, but we believe that the underlying principles that regulate why organisms die from disseminated cancer will apply to most solid tumors such as pancreatic, breast and colon cancer, for example.
A very different way of trying to treat cancer is to "teach" the body to live with the cancer cells. In this paradigm, we would not aim to kill cancer cells; instead we would teach the normal cells of the body how to avoid dying in response to the cancer cells. Although initially this sound unappealing, we all live with cancer cells at some point in our lives - our bodies are constantly generating mutated pre-cancerous cells, but these cells rarely kill us. Our studies in the zebrafish aim to identify specific genes and pathways that allow the animal to live with widely disseminated, metastatic cancer, without negatively affecting survival of the animal. Although we cannot always extrapolate from a fish to a human, we feel that by discovering these basic mechanisms of cancer tolerance, we can rapidly apply this knowledge to human patients with metastatic cancer.
The ultimate goal is two-fold: 1) understand the basic mechanisms underlying why the body can sometimes live with cancer, and 2) can we identify drugs that can educate any person to become "tolerant" to their cancer without affecting their survival?
Featured funders of this work include: NIH New Innovator, Melanoma Research Alliance, Albina Co., Inc. Research Funders crowdfunding donations will be used as follows