Keystone Cancer Cells

Polyaneuploid cancer cells (PACCs) are the keystone species of lethal cancer.

There are two central challenges to cancer survivorship:
1. Metastasis: cancer spread.
2. Therapy resistance: cancer becomes resistant to all known treatments.

Historically, these two phenomena are studied as distinct events that occur stochastically in the tumor. Our recent work suggests that this model is incomplete.

We now hypothesize that these two critical processes are likely linked by a critical cell-state transition: the polyanueploid cancer cell (PACC). These abnormally large cells with high genomic content arise in response to external stress, such as chemotherapy, and are present in all adenocarcinoma tumor types, including prostate, breast, ovarian, and lung. We have also shown that these PACCs have features of metastatic potential, including high motility.

Prostate cancer cells before (left) and after (right) chemotherapy treatment for 3 days.
Note the very large shape and increased nuclear area after treatment: PACCs.

Keystone cancer cells

We now believe that PACCs represent a keystone species in the tumor that actuate both successful metastatic seeding and therapeutic resistance. Named after the architectural element of an arch, a keystone species, though few in number, supports the essential structure of its ecosystem. Common examples of keystone species are the wolves of Yellowstone, the otters of the kelp forests in the Pacific Northwest, and the elephants of the Serengeti.

Keystone species

one that plays a critical role in maintaining its ecosystem with a disproportionally large effect relative to its abundance.