Credit: PNAS
A new model suggests we should be targeting cancers’ weaknesses instead of their strengths.
An article in BioEssays proposes that cancers form when recently evolved genes are damaged, and cancer cells have to revert to using older, inappropriate genetic pathways.
So we should create treatments that take advantage of capabilities humans have developed more recently—such as the adaptive immune system—instead of trying to target older capabilities—such as the innate immune system and cell proliferation.
“The rapid proliferation of cancer cells is an ancient, default capability that became regulated during the evolution of multicellularity about a billion years ago,” said study author Charley Lineweaver, PhD, of The Australian National University in Canberra.
“Our model suggests that cancer progression is the accumulation of damage to the more recently acquired genes. Without the regulation of these recent genes, cell physiology reverts to earlier programs, such as unregulated cell proliferation.”
To develop their model, Dr Lineweaver and his colleagues turned to knowledge uncovered by genome sequencing in a range of our distant relatives, including fish, coral, and sponges.
This knowledge has allowed scientists to establish the order in which genes evolved and is the basis of the new therapeutic implications of the model, Dr Lineweaver said.
He noted that the standard model of cancer development suggests that selection produces the acquired capabilities of cancer—such as sustained proliferative signaling and evading apoptosis—and they evolve during the lifetime of the patient.
But Dr Lineweaver’s model suggests the capabilities of cancer are acquired atavisms. They are activated during early embryogenesis and wound healing and reactivated inappropriately during carcinogenesis.
The most recent capabilities—mammalian and vertebrate capabilities—are the least entrenched in cancer. So they should be targeted with therapy.
The older capabilities—last eukaryotic common ancestor (LECA) capabilities, stem eukaryote capabilities, and the earliest evolved capabilities—are maintained in cancer and are therefore difficult to target.
For example, some human ATP binding cassette (ABC) transporters are ancient, and some are quite recent. Dr Lineweaver and his colleagues found that older ABC proteins were more likely to be active in cancer.
So the researchers believe we should create treatments that can be expelled by the newer ABC transporters. That way, normal cells will expel the treatment, but cancer cells will not.
Another potential treatment avenue, according to Dr Lineweaver, is targeting the adaptive immune system.
“The adaptive immune system that humans have has evolved relatively recently, and it seems cancer cells do not have the ability to talk to and be protected by it,” he noted.
“The new therapeutic strategies we are proposing target these weaknesses. These strategies are very different from current therapies, which attack cancer’s strength—its ability to proliferate rapidly.”
