Aspirin may strengthen anti-cancer drugs

December 07, 2017
Top News in Oncology #5 of 6

Healthline/Medical News Today

Adding aspirin to a particular cancer medication increases its effectiveness against some cancers. These latest findings offer hope for individuals with certain difficult-to-treat cancers.
Finding a “cure” for cancer is the Holy Grail of medical research. However, a single catch-all solution is unlikely; cancer comes in many shapes and forms.
Each type of cancer involves different cell types and cellular environments, mutations in a range of genes, and alterations to the way specific cells function; this makes understanding and treating cancer a complex battle.
Some researchers have referred to cancer as a “constellation” of diseases.
One particular type of cancer, which has mutations in a set of genes called RAS, is a particularly challenging type to treat.
Cancers with RAS mutations include some pancreatic, colorectal, and lung cancers, and a small number of melanomas; they have low survival rates. Currently, there are no pharmaceuticals specifically designed to target RAS mutant cancers.
One drug—Sorafenib—showed “marginal” benefits in a multicenter Phase 3 trial for one type of lung cancer. However, side effects were significant, causing some patients to drop out of the trial early.
Aspirin and cancer
Aspirin, or acetylsalicylic acid, has been used in one form or another since ancient times. For instance, Hippocrates referred to the use of salicylic tea to reduce fevers around 400 B.C. Aspirin is still used to treat a range of medical complaints.
Today, it is available over the counter and used to relieve pain and reduce fever. It is also prescribed to individuals who have had heart attacks and strokes as it significantly reduces the risk of another cardiovascular event.
Other research has found that aspirin has certain anti-cancer effects; this protective action seems particularly pronounced in colorectal cancers.
With this relationship in mind, scientists from the University of Queensland in Australia recently set out to investigate whether adding aspirin to Sorafenib could increase its potency in cancers with RAS mutations.
The research team, led by Associate Professor Helmut Schaider, published their results this week in the journal Clinical Cancer Research. Using a mouse model, the results were encouraging.

“We found the addition of aspirin to a cancer inhibitor drug, Sorafenib, strongly enhanced its effectiveness against mouse models of lung cancer and melanoma with RAS mutations.”
Dr. Helmut Schaider

Drilling down into the details, the scientists examined the molecular mechanisms that facilitated aspirin’s positive effects. Dr. Schaider explains how the addition of a relatively high aspirin dose appears to improve outcomes:
“Two molecular processes are activated and together they work to kill RAS mutant cancer cells. This dual activation also might prevent the tumors acquiring resistance to the treatment, which can happen when the inhibitor drug is given alone.”
The future of Sorafenib and aspirin
The researchers believe that taking the drugs in combination may mean that patients could take Sorafenib in smaller doses, reducing the negative consequences of side effects.
The combination has the potential to extend the length of time cancer patients have without the disease progressing. Dr. Schaider says that “adding aspirin could also potentially prevent relapse of tumors in patients.”
The next step is to investigate whether this positive interaction can be demonstrated in human patients; hopefully, follow-up work will not be too far down the line, as Dr. Schaider says:
“A clinical trial of the combination could proceed relatively quickly, potentially piggy-backing on other testing already underway.”
However, the adverse effects of taking high doses of aspirin would need to be managed; for instance, the chance of excessive bleeding is increased. For individuals with no other treatment options, however, the negative impacts of aspirin would be outweighed by the benefits.
Work is already underway to understand whether aspirin in conjunction with other cancer drugs might increase outcomes. If aspirin can impart a genuine benefit, it would be a significant and cost-effective step forward in cancer treatment.

Aspirin could boost immune response to cancer

John Murphy, MDLinx, 09/08/2015
Adding aspirin to immunotherapy could greatly improve cancer treatment, according to a new study published online September 3, 2015 in Cell.

Aspirin could halt cancer cells’ protective barrier and unleash the full power of the immune system.

The study builds on research that tumor cells are often able to evade the immune system, although how tumor cells do this is not fully understood. But prior research has found that cyclooxygenase (COX) in tumors produces prostaglandin E2 (PGE2), which is associated with enhanced cancer cell survival, growth, migration, and immunosuppression.
In this study, researchers determined that melanoma, colorectal, and breast cancers produce excess PGE2, which suppresses tumor immunity and induces inflammation associated with cancer progression.
“We’ve added to the growing evidence that some cancers produce PGE2 as a way of escaping the immune system,” said study author Caetano Reis e Sousa, DPhil, senior group leader at the Francis Crick Institute in London, U.K. “If you can take away cancer cells’ ability to make PGE2, you effectively lift this protective barrier and unleash the full power of the immune system.”
Asprin, a COX inhibitor, could stop the production of PGE2, which would prevent tumors from evading the immune system. When the researchers tested it in mice, they found that aspirin combined with an immune checkpoint blocker (anti-PD-1 monoclonal antibody) substantially slowed melanoma and colorectal cancer growth, compared with immunotherapy alone.
“Giving patients COX inhibitors like aspirin at the same time as immunotherapy could potentially make a huge difference to the benefit they get from treatment,” said Dr. Reis e Sousa. “It’s still early work but this could help make cancer immunotherapy even more effective, delivering life-changing results for patients.”