Keystone Cancer Cells
Why are cancers resistant to all treatments?
Our Audacious idea is to cure cancer. Despite decades of research, cancer kills more than 9 million people worldwide annually. While cancer is cured if found locally, metastatic disease remains incurable because cancer cells in a tumor develop resistance to all known natural and synthetic compounds. Resistance to therapy is both present in a treatment-naïve setting, as well as further induced through therapeutic treatment. Despite decades of research, the source of this resistance remains undefined. Recently, we have discovered the reason for this resistance and believe we can initiate an Audacious Project to eradicate metastatic cancer. In our experiments using a unique imaging system that allowed longitudinal visualization of cancer cell populations responding to treatment we discovered a subtype of cancer cells that are giant, multi-nucleated, and have elevated genomic content that are capable of surviving in toxic levels of all therapies and subsequently repopulate tumors with now resistant cells. We have now demonstrated that these giant cells exist in cancer patients, “hiding” as a small fraction of the general population of cancer cells, acting as a keystone species playing critical roles to maintain tumors. Unless these cells are targeted and eliminated, cancer is not curable.
To cure cancer, we now know for the first time that we must eliminate the keystone giant cells that are the source of therapeutic resistance. Using ecological principles, we have developed a multipronged approach to rapidly understand and eradicate these cells, bringing together and synergizing the expertise of investigators drawn from several different fields, including cancer biology, ecology, physics, mathematics, developmental biology, protein chemistry, medical oncology, radiation oncology, stem cell biology, drug development, genomics, and immunology, all driven by this common goal.