One of the reasons that cancer is so hard to beat is the way that it ropes our immune system into working against us. Treatment kills off some cancer cells, but what's left behind can "trick" our immune system into helping tumors to form. New research may have found a way to break this vicious circle.
This occurs because the cellular debris that is left behind triggers an inflammatory response from our immune system, which, in turn, can stimulate the production of more cancer cells.
But researchers may now have found a way out of this conundrum. A new study has found that resolvins — compounds naturally secreted by our body in order to stop the inflammatory response — can stop tumors from growing when such growth is induced by cellular waste.
The research was led by Sui Huang, from the Institute of Systems Biology in Seattle, WA, as well as Charles N. Serhan, from the Brigham and Women's Hospital at Harvard Medical School, Mark Kieran, from the Dana-Farber Cancer Institute, and Dipak Panigrahy, from the Beth Israel Deaconess Medical Center, all of which are in Boston, MA.
Megan Sulciner is the first author of the paper, and the findings were published in The Journal of Experimental Medicine.
Conventional therapy's 'double-edged sword'
Sulciner and her colleagues used cytotoxic treatment and other targeted drugs to kill off laboratory-cultured cancer cells. The resulting cellular debris was injected into mice. The rodents already had a few cancer cells in them, but these were not enough to promote tumor growth on their own.
The researchers also treated mice with traditional chemotherapy drugs.
Both approaches stimulated the spread of cancer cells and boosted their ability to grow tumors. Debris-induced tumor growth could be seen both in vivo and in the cultured cells.
The study revealed that a lipid called phosphatidylserine — which is found on the surface of dead and stressed cells — makes the immune cells release pro-inflammatory cytokines.
The lead study authors spoke to Medical News Today about their findings and the mechanisms underlying them.
"Our studies," they explained, "along with others, show that traditional cancer therapy may be a 'double-edged sword,' wherein the very treatment used to cure cancer is also helping it survive and grow."
Although aimed at killing cancer cells, these therapies leave behind "tumor cell debris," which, the researchers explained, "generates a 'cytokine storm' of pro-inflammatory pro-tumorigenic cytokines."
The few cancer cells that do survive treatment, "combined with an inflammatory setting induced by tumor cell debris, may result in the 'perfect storm' for cancer progression. Therefore, conventional chemotherapy [...] may contribute to tumor relapse," explained the authors.
"The findings underscore the old idea that killing cancer cells with more and more effective drugs may backfire," added Huang.
"The tumor tissue is a reactive system that turns cell-killing therapy into double-edge[d] swords: the more you kill the more you may stimulate the surviving tumor cells," he added.
Huang explained, "Dead-cell stimulated growth is naturally a part of the tissue regeneration cycle; debris is interpreted by the tissue as injury signal and stimulates wound healing and regeneration."
"Whether a cytotoxic treatment is successful or not," he added, "hinges on hitting a small window of opportunity: when the net kill effect is stronger than the stimulatory of the dead cells that treatment creates."
The study's lead authors said:
"Overcoming the dilemma of debris-induced tumor progression is paramount if we are to prevent tumor recurrence of treatment-resistant tumors — the major reason for [the] failure of cancer therapy."
Resolvins 'kill cancer gently'
In order to address the challenge of this double-edged sword, the researchers treated the rodents with small amounts of resolvins. Resolvins are "a natural product of tissue that serves as a stop signal to end the inflammatory process," the authors told MNT.
These chemical compounds were, in fact, discovered in a study led by co-lead study author Serhan a few years ago.
The treatment with resolvins stopped the debris-induced tumor growth and blocked the cancer cells from spreading. Additionally, resolvins boosted the activity of various anti-cancer drugs, making them more effective in their fight against tumors.
Huang also spoke to MNT about the clinical implications of the study:
"In brief, we learn that when it comes to cancer therapy: 'Thou shall not kill — or kill gently and remove dead bodies immediately.'"
"[T]his means that gentler killing or stopping the endless run-away regeneration cycle could be useful: this naturally leads to the use of inflammation-clearing resolvins," he added.
Resolvins are already being clinically tested for their therapeutic properties in other illnesses, the authors note.
Huang says, "Targeting the resolvin pathways provides an entirely new, non-toxic, and non-immunosuppressive approach to cancer therapy."
Huang also shared with MNT readers some of their directions for future research, saying, "We need to find evidence from clinical studies that the same principles that we found in mice (although using human cells in some cases) [apply] to human cancer."