Keystone Cancer Cells: Polyaneuploid Cancer Cells
![A Keystone Cancer cell. A keystone species is a plant or animal that plays a unique and crucial role in the way an ecosystem functions. These keystone cancer cells enter a state that is simultaneously polyploid and aneuploid (polyaneuploid cancer cells [PACCs]), that avoid the toxic effects of systemic therapy by entering a state of cell cycle arrest.](https://images.squarespace-cdn.com/content/v1/5862977020099ed7751900b0/1555636869067-QJRUB7XDVIPZUR70XXNE/Slide1.jpeg)
A Keystone Cancer cell. A keystone species is a plant or animal that plays a unique and crucial role in the way an ecosystem functions. These keystone cancer cells enter a state that is simultaneously polyploid and aneuploid (polyaneuploid cancer cells [PACCs]), that avoid the toxic effects of systemic therapy by entering a state of cell cycle arrest.
Why are all cancers resistant to systemic therapies?
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 that some cancer cells have the ability to enter into state that is marked by the cells being very large and having elevated genomic content. In this state, the cells are capable of surviving in toxic levels of all therapies and subsequently repopulate tumors with progeny that are resistant to therapy. We have now demonstrated that these special 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. We have termed these Keystone cells “PolyAneuploid Cancer Cells (PACCs)”.
To cure cancer, we now know for the first time that we must eliminate the keystone 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.