Aspirin may be able to dramatically reduce tumor growth in colorectal cancer patients, especially if they have genetic mutations in a certain gene. A Harvard-led research team published a study along those lines recently in the New England Journal of Medicine, and UAB oncologist Boris Pasche was asked to write an editorial on the study.
According to a recent UAB News article, the study separated patients with colorectal cancer into two groups: one with a missing or mutated version of the gene PIK3CA, and another with the functioning gene in place. The use of aspirin in patients with the gene mutation was associated with a dramatic 46 percent reduction in overall mortality and an 82 percent reduction in colorectal cancer-specific mortality. In contrast, aspirin use in patients without the mutation did not affect mortality.
With about one in six of the 140,000 patients diagnosed with this cancer each year, carrying a mutated PIK3CA gene, the impact of the study could be considerable.
Dr. Pasche is quick to point out, however, that the findings are still early. Larger, controlled studies will be needed before the work changes clinical practice, but the results once again argue for the value of genetic research in personalized medicine.
The Mix sat down with Dr. Pasche, director of the UAB Division of Hematology and Oncology within the UAB School of Medicine to get his take on the study, its importance and limitations.
Show notes for the podcast
1:05 Over the past decade, little progress has been made in the treatment of locally advanced colorectal cancer, cancer that has spread to nearby lymph nodes but has not metastasized, or spread to other organs.While several new drugs have proven useful in the treatment of metastatic colorectal cancer, only one of them has demonstrated efficacy in locally advanced colorectal cancer.
1:25 A number of studies over the years had found that patients taking aspirin after a diagnosis of colon were less likely to die over time (lower mortality) than those not taking aspirin.
2:11 More recently, several studies further showed that patients taking aspirin (because it is already known to protect against heart disease) had a lower risk of colon cancer metastases. Others suggested that aspirin may also prevent the spread of established cancer and prevent recurrence in a significant group of patients.
2:43 A major question has been which patients will benefit from aspirin therapy. A study published a few years ago in the Journal of the American Medical Association. by the same investigators at Harvard identified COX2 as one molecular signalling pathway that was overactive in colon cancer patients that benefited from aspirin therapy.
This makes sense because COX2 is an inflammatory pathway, and aspirin is known to block it.
3:12 The Harvard team's latest study set out to pinpoint the mechanisms by which aspirin therapy changed the action of genes known to influence the COX2 pathway. It turns out that a gene called PIK3CA may be an important arbiter in determining whether or not aspirin helps a given person fend off colon cancer.
3:27 The use of aspirin in patients with the gene mutation was associated with an 82 percent reduction in colorectal cancer-specific mortality. In contrast, aspirin use in patients without the mutation did not affect mortality. Why this is so remains to be seen.
4:00 The work represents, in Pasche's view,. an ongoing trend, where a better understanding of molecular pathways surrounding disease re-positions old drugs as targeted, 21st Century therapies that work tremendously well for people with the right genetic profile.
4:45 In recent years, researchers found that patients with colon cancer frequently had developed mutations, small, random changes, in their version of the code for the gene called PIK3CA. Like many mutations though, it made no difference in whether or not patients were more likely to survive. Only in combination with aspirin therapy did this genetic difference become valuable.
6:00 The Harvard study measured both overall mortality (overall likelihood to die in general in a given time period) and colon-cancer specific mortality with respect to patients having the mutation and taking aspirin. Measuring both helps to confirm or dismiss the idea that a treatment is making people live longer by countering cancer specifically, versus just making people live longer through some general mechanism.
6:50 While this early study is in a very small number of patients, its results are intriguing, says Pasche, and he expects larger, randomized, follow-up studies to follow quickly.
8:24 Should the use of aspirin be validated, its addition would be welcome, says Pasche. Over the past decade, little progress has been made in the treatment of locally advanced colorectal cancer, which is defined as cancer that has spread to nearby tissue or lymph nodes but has not metastasized, or spread to other organs. While several new drugs have proven useful in the treatment of metastatic colorectal cancer, only one of them addresses local cancer that has advance. More options are needed.
11:27 One cause for concern is that aspirin is known to increase the risk of gastrointestinal bleeding and hemorrhagic strokes, but Pasche argues that it is among the most safe and well tolerated of drugs currently used in oncology.
For more information, visit the UAB Comprehensive Cancer Center site.