Aspirin cuts colorectal cancer recurrence risk by half in individuals with certain genetic markers among high risk individuals

Good news! Cancer is history (soon)! This was a three year long study!

Good old Aspirin keeps on giving! I take one baby/low dose Aspirin (81 mg) pill basically every day since about the year 1999. My last colonoscopy did find anything.

"A study involving more than 1,000 cancer patients has found that a low dose of aspirin halves the risk of colorectal tumors returning after surgery. This readily available and inexpensive treatment could change health outcomes for a significant number of cancer survivors who have problematic gene variants. ...

Researchers ... screened 3,508 patients with stage I, II, or III rectal cancer or stage II or III colon cancer, finding that 1,103 of these people had a specific variant in the PI3K pathway – the genetic marker of interest. The team then conducted a double-blind, randomized, placebo-controlled trial on this gene-altered cohort, with 626 patients receiving 160-mg aspirin daily for three years and the remainder taking a placebo.

This study, known as the ALASCCA trial, was a massive effort involving 33 hospitals in Sweden, Norway, Denmark and Finland. The team prioritized people with the PIK3CA gene mutation, as well as people with other moderate or high impact variants in PIK3R1 and PTEN. ...

What they found was that for people with the genetic mutation in PIK3, aspirin lowered the risk of recurrence by 55% compared with placebo treatment. ..."

From the abstract:

"Background

Aspirin reduces the incidence of colorectal adenoma and colorectal cancer among high-risk persons. Observational studies suggest that aspirin may also improve disease-free survival after diagnosis, particularly among patients with tumors harboring somatic PIK3CA mutations. However, data from randomized trials are lacking.

Methods

We conducted a double-blind, randomized, placebo-controlled trial involving patients with stage I, II, or III rectal cancer or stage II or III colon cancer with somatic alterations in PI3K pathway genes. The patients were assigned in a 1:1 ratio to receive 160 mg of aspirin or matched placebo once daily for 3 years. Patients with prespecified PIK3CA hotspot mutations in exon 9 or 20 (group A alterations) and those with other moderate- or high-impact somatic variants in PIK3CA, PIK3R1, or PTEN (group B alterations) were eligible for randomization. The primary endpoint was colorectal cancer recurrence, assessed in a time-to-event analysis, in patients with group A alterations. Secondary end points included colorectal cancer recurrence in patients with group B alterations, disease-free survival, and safety.

Research Summary

Results

Alterations in PI3K pathway genes were detected in 1103 of 2980 patients (37.0%) with complete genomic data.

Of 515 patients with group A alterations and 588 patients with group B alterations, 314 and 312, respectively, were assigned to receive aspirin or placebo.

The estimated 3-year cumulative incidence of recurrence was 7.7% with aspirin and 14.1% with placebo (hazard ratio, 0.49; 95% confidence interval [CI], 0.24 to 0.98; P=0.04) among patients with group A alterations and 7.7% and 16.8%, respectively (hazard ratio, 0.42; 95% CI, 0.21 to 0.83), among those with group B alterations.

The estimated 3-year disease-free survival was 88.5% with aspirin and 81.4% with placebo (hazard ratio, 0.61; 95% CI, 0.34 to 1.08) among patients with group A alterations and 89.1% and 78.7%, respectively (hazard ratio, 0.51; 95% CI, 0.29 to 0.88), among those with group B alterations. 

Severe adverse events occurred in 16.8% of aspirin recipients and 11.6% of placebo recipients.

Conclusions

Aspirin led to a significantly lower incidence of colorectal cancer recurrence than placebo among patients with PIK3CA hotspot mutations in exon 9 or 20 and appeared to have a similar benefit among those with other somatic alterations in PI3K pathway genes. ..."

Aspirin cuts colorectal cancer recurrence risk by half

Common inexpensive drug halves recurrence in colorectal cancer (original news release) "A Swedish-led research team at Karolinska Institutet and Karolinska University Hospital has shown in a new randomized clinical trial that a low dose of the well-known medicine aspirin halves the risk of recurrence after surgery in patients with colon and rectal cancer with a certain type of genetic alteration in the tumor."

Low-Dose Aspirin for PI3K-Altered Localized Colorectal Cancer (no public access)

Scientists discover how aspirin could prevent some cancers from spreading

Good news! Cancer is history (soon)!

Just amazing how good old aspirin keeps on giving! When I take my next low dose aspirin today, I will feel much better immediately!

"... Studies of people with cancer have previously observed that those taking daily low-dose aspirin have a reduction in the spread of some cancers, such as breast, bowel, and prostate cancers, leading to ongoing clinical trials. However, until now it wasn’t known exactly how aspirin could prevent metastases. ...

The researchers determined that ARHGEF1 suppresses a type of immune cell called a T cell, which can recognise and kill metastatic cancer cells. 

To develop treatments to take advantage of this discovery, they needed to find a way for drugs to target it. The scientists traced signals in the cell to determine that ARHGEF1 is switched on when T cells are exposed to a clotting factor called thromboxane A2 (TXA2).

This was an unexpected revelation for the scientists, because TXA2 is already well-known and linked to how aspirin works. ..."

From the abstract:

"Metastasis is the spread of cancer cells from primary tumours to distant organs and is the cause of 90% of cancer deaths globally. Metastasizing cancer cells are uniquely vulnerable to immune attack, as they are initially deprived of the immunosuppressive microenvironment found within established tumours. There is interest in therapeutically exploiting this immune vulnerability to prevent recurrence in patients with early cancer at risk of metastasis.

Here we show that inhibitors of cyclooxygenase 1 (COX-1), including aspirin, enhance immunity to cancer metastasis by releasing T cells from suppression by platelet-derived thromboxane A2 (TXA2). TXA2 acts on T cells to trigger an immunosuppressive pathway that is dependent on the guanine exchange factor ARHGEF1, suppressing T cell receptor-driven kinase signalling, proliferation and effector functions. T cell-specific conditional deletion of Arhgef1 in mice increases T cell activation at the metastatic site, provoking immune-mediated rejection of lung and liver metastases.

Consequently, restricting the availability of TXA2 using aspirin, selective COX-1 inhibitors or platelet-specific deletion of COX-1 reduces the rate of metastasis in a manner that is dependent on T cell-intrinsic expression of ARHGEF1 and signalling by TXA2 in vivo.

These findings reveal a novel immunosuppressive pathway that limits T cell immunity to cancer metastasis, providing mechanistic insights into the anti-metastatic activity of aspirin and paving the way for more effective anti-metastatic immunotherapies."

Scientists discover how aspirin could prevent some cancers from spreading | University of Cambridge "Scientists have uncovered the mechanism behind how aspirin could reduce the metastasis of some cancers by stimulating the immune system."

Aspirin prevents metastasis by limiting platelet TXA2 suppression of T cell immunity (open access)

Fig. 5: Aspirin promotes anti-metastatic immunity by releasing T cells from ARHGEF1-dependent suppression by TXA2.

Aspirin cuts liver fat in trial

The good old Aspirin (in use for over 2,400 years) keeps on giving! I look forward to take my daily baby (low dose) Aspirin later today! 😊 Long live the liver!

"... In their Phase 2 trial, 80 adults with MASLD were randomized to receive daily low-dose aspirin or placebo for six months. At the end of the study, the average change in liver fat content was minus 6.6 percent with aspirin versus plus 3.6 percent with placebo, showing that low-dose aspirin reduced the average liver fat content by 10.2 percent compared with placebo. The aspirin was found to be safe and well-tolerated, and also improved various markers of liver health. ..."

From the key points and abstract:

"Key Points

Question

In patients with metabolic dysfunction–associated steatotic liver disease (MASLD), does 81 mg of aspirin daily reduce the quantity of hepatic fat at 6-month follow-up compared with placebo?

Findings

In this phase 2 randomized clinical trial of 80 individuals with MASLD, daily aspirin reduced the quantity of hepatic fat at 6-month follow-up compared with placebo (mean difference, −10.2%).

Meaning

In a preliminary randomized clinical trial of adults with MASLD, 6 months of daily low-dose aspirin significantly reduced liver fat content compared with placebo, but findings are preliminary and require confirmation in a larger population.

Abstract

Importance

Aspirin may reduce severity of metabolic dysfunction–associated steatotic liver disease (MASLD) and lower the incidence of end-stage liver disease and hepatocellular carcinoma, in patients with MASLD. However, the effect of aspirin on MASLD is unknown.

Objective

To test whether low-dose aspirin reduces liver fat content, compared with placebo, in adults with MASLD.

Design, Setting, and Participants

This 6-month, phase 2, randomized, double-blind, placebo-controlled clinical trial was conducted at a single hospital in Boston, Massachusetts. Participants were aged 18 to 70 years with established MASLD without cirrhosis. Enrollment occurred between August 20, 2019, and July 19, 2022, with final follow-up on February 23, 2023.

Interventions

Participants were randomized (1:1) to receive either once-daily aspirin, 81 mg (n = 40) or identical placebo pills (n = 40) for 6 months.

Main Outcomes and Measures

The primary end point was mean absolute change in hepatic fat content, measured by proton magnetic resonance spectroscopy (MRS) at 6-month follow-up. The 4 key secondary outcomes included mean percentage change in hepatic fat content by MRS, the proportion achieving at least 30% reduction in hepatic fat, and the mean absolute and relative reductions in hepatic fat content, measured by magnetic resonance imaging proton density fat fraction (MRI-PDFF). Analyses adjusted for the baseline value of the corresponding outcome. Minimal clinically important differences for study outcomes were not prespecified.

Results

Among 80 randomized participants (mean age, 48 years; 44 [55%] women; mean hepatic fat content, 35% [indicating moderate steatosis]), 71 (89%) completed 6-month follow-up. The mean absolute change in hepatic fat content by MRS was −6.6% with aspirin vs 3.6% with placebo (difference, −10.2% [95% CI, −27.7% to −2.6%]; P = .009). Compared with placebo, aspirin treatment significantly reduced relative hepatic fat content (−8.8 vs 30.0 percentage points; mean difference, −38.8 percentage points [95% CI, −66.7 to −10.8]; P = .007), increased the proportion of patients with 30% or greater relative reduction in hepatic fat (42.5% vs 12.5%; mean difference, 30.0% [95% CI, 11.6% to 48.4%]; P = .006), reduced absolute hepatic fat content by MRI-PDFF (−2.7% vs 0.9%; mean difference, −3.7% [95% CI, −6.1% to −1.2%]; P = .004]), and reduced relative hepatic fat content by MRI-PDFF (−11.7 vs 15.7 percentage points; mean difference, −27.3 percentage points [95% CI, −45.2 to −9.4]; P = .003). Thirteen participants (32.5%) in each group experienced an adverse event, most commonly upper respiratory tract infections (10.0% in each group) or arthralgias (5.0% for aspirin vs 7.5% for placebo). One participant randomized to aspirin (2.5%) experienced drug-related heartburn.

Conclusions and Relevance

In this preliminary randomized clinical trial of patients with MASLD, 6 months of daily low-dose aspirin significantly reduced hepatic fat quantity compared with placebo. Further study in a larger sample size is necessary to confirm these findings."

Aspirin cuts liver fat in trial — Harvard Gazette 10 percent reduction seen in small study of disease that affects up to a third of U.S. adults

Aspirin for Metabolic Dysfunction–Associated Steatotic Liver Disease Without Cirrhosis (no public access)

Aspirin newsworthy again, a perennial medication

A journey that started 2400 years ago, Aspirin is in the news again twice lately!

Like a fashion, the opinions on Aspirin wax and wane, up and down, and resurge again!

As for me, I will continue to take my 81mg Aspirin tablet almost daily! 😄

I did not have the time to read through the draft recommendations (it's a pretty dry text with lots of medical language), but I sense some of these underlying medical studies focused on when Aspirin medication was initiated in life. It appears, when initiated very late in life like after 60-65 then the negative effects may outweigh the positive ones.

Aspirin lowers risk of COVID: New findings support preliminary trial - The Jerusalem Post The treatment reduced the risk of reaching mechanical ventilation by 44%. ICU admissions were lower by 43%, and an overall in-hospital mortality saw a 47% decrease.

Aspirin No Longer Recommended as a Preventative Measure Against Heart Attacks and Strokes in Older Individuals The guideline change is based on bleeding risks some may face when taking the blood thinner

Draft Recommendation Statement Aspirin Use to Prevent Cardiovascular Disease: Preventive Medication

Aspirin users may have protection against Covid-19

One more good reason to pop you daily baby Aspirin tablet!

"Healthy people taking aspirin regularly to prevent cardiovascular disease had a 29 percent lower likelihood of Covid-19 infection compared to aspirin non-users, according to an observational epidemiological study from Israel published in The FEBS Journal.

Researchers from Leumit Health Services, Bar-Ilan University and Barzilai Medical Center analyzed data of 10,477 members of the Leumit HMO who had been tested for Covid-19 from February 1, 2020 to June 30, 2020.

They knew that aspirin was widely used during the 1918 Spanish influenza pandemic several decades before its activity against RNA viruses was understood.

They were also aware of studies showing that aspirin, in addition to reducing inflammation, can help the immune system battle some viral infections. ..."

Aspirin users may have protection against Covid-19 - ISRAEL21c People taking aspirin regularly to prevent cardiovascular disease could have reduced likelihood of Covid-19 infection and shorter duration of disease.

Here is the link to the referenced paper:

The use of aspirin for primary prevention of cardiovascular disease is associated with a lower likelihood of COVID‐19 infection

SMAR1 repression by pluripotency factors and consequent chemoresistance in breast cancer stem-like cells is reversed by aspirin | Science Signaling

If there is anything that deserves the moniker wonder drug it ought to be Aspirin!

"... Treating cultured CSCs or 4T1 tumor-bearing mice with the nonsteroidal anti-inflammatory drug aspirin restored SMAR1 expression and ABCG2 repression and enhanced tumor sensitivity to doxorubicin. ..."

SMAR1 repression by pluripotency factors and consequent chemoresistance in breast cancer stem-like cells is reversed by aspirin | Science Signaling