In a recent review published in Open Biology, researchers discussed the existing evidence on the use of acetylsalicylic acid (aspirin) in cancer treatment. They conducted a literature review to understand how aspirin influences biological mechanisms in cancer and summarized the findings from clinical trials and observational studies involving aspirin in cancer treatment.
Study: Aspirin and cancer: biological mechanisms and clinical outcomes. Image Credit: fizkes/Shutterstock
Background
Botanical resources and active plant components have long been a source of potential cancer treatments. The potency of salicylates in regulating the responses to biotic and abiotic stress and defending plants against various pathogens has been established through years of research.
Given the prevalence of cancer-related deaths, especially in undeveloped countries with poor access to diagnostic and treatment options, there is a vital need for affordable and accessible cancer therapy. Developing novel anti-cancer drugs is expensive and tedious, with clinical trials that may not always be successful. Therefore, exploring existing approved drugs for cancer treatment is growing.
Acetylsalicylic acid, or aspirin, is an anti-inflammatory and analgesic drug commonly used against pain and fever in various diseases. Some biological mechanisms regulated by aspirin also play a role in cancer initiation and growth, making it a useful anti-cancer therapeutic option.
About the study
In the present study, the researchers used a systematic literature review to address three major aspects of the use of aspirin in cancer therapy. They first summarized the current findings on the biological mechanisms through which aspirin can regulate cellular level pathogenic pathways and metastatic processes in cancer.
The review then examined various clinical studies to understand the effect of aspirin on cancer metastasis and survival. Lastly, the researchers addressed the known side effects of aspirin use, such as intracranial and gastrointestinal bleeding, and commented on the safety aspects of using aspirin in cancer therapy.
Main findings
The review reported a multitude of pathways through which aspirin could potentially play a role in anti-cancer therapy. The primary mode of action of aspirin is through cyclooxygenase (COX) enzyme disruption, which inhibits the formation of cancer signaling molecules like prostanoids. Aspirin also interrupts proliferative and inflammatory pathways and interferes with platelet-driven pro-carcinogenic processes.
Angiogenesis, or the formation of new blood vessels, is an important part of cancer progression. Studies on lymphoma and colon cancer cell lines showed that aspirin prevents angiogenesis by disrupting the COX enzyme and regulating the activity of vascular endothelial growth factor (VEGF). Additionally, aspirin stimulates pro-apoptotic pathways and promotes tumor suppressor gene-mediated deoxyribonucleic acid (DNA) repair.
Studies on metastasis using in vivo animal models and in vitro cell lines have shown that platelets play a major role in enabling metastatic migration by secreting growth factors, promoting metastatic niche formation, and producing inhibitors of tumor suppressor genes. Aspirin displayed anti-platelet activity, which reduced the metastasis in many in vivo animal models. Research using proteomics and gene-environment interactions also provided evidence of aspirin downregulating the expression of DNA repair genes, whose overexpression has been linked to increased colon cancer risk.
The overall evidence from clinical and observational studies is favorable regarding the use of aspirin in anti-cancer therapy, despite the high heterogeneity. However, the authors highlighted the absence of ad hoc randomized trials exploring the effect of aspirin on a wide range of cancers. Most of the evidence comes from meta-analyses of observational data from individuals with different types of cancers, a quarter of whom were taking aspirin.
According to the authors, many studies have focused on common cancers such as lung, breast, prostate, and colon cancer, that account for only 30% of the worldwide cancer cases, leaving the rarer forms of cancer understudied.
Aspirin use has also been linked to increased gastrointestinal and cerebral bleeding due to its anti-platelet activity. While quite a few studies reported fatal bleeds linked to aspirin use, especially in older patients, one interpretation of the results also suggests that aspirin’s anti-platelet action is uncovering existing gastrointestinal pathologies such as gastric lesions, which can then be treated.
Conclusions
Overall, the study indicates that aspirin’s role in regulating various metabolic pathways makes it a potentially valuable and viable anti-cancer treatment option. However, most of the current evidence of its efficacy in reducing tumor cell proliferation and metastasis comes from four ad hoc randomized trials. Therefore, more research is needed on the use of aspirin in the treatment of some of the rarer forms of cancer. Comprehensive research into the adverse effects of aspirin is also required before promoting the use of aspirin in cancer therapy.
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