PD-1 Blockade Treatment shows 100% Tumor Resolution in Mismatch Repair Deficient Rectal Cancer Patients

Rectal cancer cases are rising in young adults (1). Typically, these cancers are treated with a multipronged approach that includes chemotherapy, radiation and surgery. These treatments show complete response in approximately 25% of patients and come with a long list of toxic side effects and life-altering complications including negative effects on bladder and bowel function, sexual health and fertility issues (2). 

artistic image of cancer cell and immunotherapeutic agents such as PD-1 blockade

Approximately 5–10% of rectal cancers have deficiencies in their mismatch repair mechanisms (dMMR), and these cancers tend to be less responsive to standard chemotherapy treatments (2). Tumors are identified as dMMR using either immunohistochemistry (IHC) to detect the presence or absence of the major mismatch repair proteins, or by molecular testing for high-frequency microsatellite instability (MSI-H), the functional evidence of dMMR . These tumors often have somatic mutations that produce “foreign” proteins that can be detected by the immune system. As a result, these tumors are effective at priming an immune response and tend to respond well to immune checkpoint therapies such as PD-1 blockade treatments. Immune checkpoint blockade, or immune checkpoint inhibitor, therapies are a revolutionary, and relatively new, approach to treating cancer. Some tumors express immune checkpoints to prevent the immune system from producing a strong enough immune response to kill the cancer cells. Immune checkpoint blockade therapies work by blocking immune checkpoint proteins that act to negatively regulate the immune system through the PD-1 pathway. When these checkpoint proteins are blocked, the body’s T-cells can recognize and kill the cancer cells.

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Protecting Pollinators: What is All the Buzz About “No Mow May”?

Pollinators A bee pollinating a wildflowers

Ah summer. The time for lazy afternoons spent dozing in a hammock, lulled to sleep by the quiet buzz of bees hard at work collecting nectar and pollen from the first flowers of the year. It sounds idyllic, but unfortunately such afternoons are falling increasingly silent. As uniformly green lawns replace patchworks of dandelions and clover, the bees are disappearing.

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Volunteering. A Celebration of Service, Community and Connection

Promega Madison employees volunteering to gather trash from roadside ditches.
Promega Madison employees gather trash from roadside ditches.

Volunteering is willingly giving your time and effort without expecting something in return. The month of April is volunteer month, and April 20 is national volunteer recognition day, so we are taking this chance to celebrate volunteers and the work they do that benefits us all. Fundamentally, volunteering is about service to others, but that service can take on many different forms. Promega recognizes the benefits that volunteering brings to our employees as well as our local and global communities. Our Promega in Action program offers Madison-based employees the chance to volunteer their time and talents; applicants get up to 40 hours of extra paid time off to work with the charity or organization of their choice.

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New Study Suggests Long Mononucleotide Repeat Markers Offer Advantages for Detecting Microsatellite Instability in Multiple Cancers

A new study, published in the Journal of Molecular Diagnostics (1), highlights the potential of using long mononucleotide repeat (LMR) markers for characterizing microsatellite instability (MSI) in several tumor types. The paper is a result of a collaborative effort between researchers from Johns Hopkins University and Promega to evaluate the performance of a panel of novel LMR markers for determining MSI status of colorectal, endometrial and prostate tumor samples.

Microsatellite instability (MSI) is the accumulation of insertion or deletion errors at microsatellites, which are short tandem repeats of DNA sequences found throughout the genome. MSI in cancerous cells is the result of a functional deficiency within one or more major DNA mismatch repair proteins (dMMR). PCR-based MSI testing is a commonly used method that can help understand a tumor’s genomic profile as it relates to MMR protein function.

Historically, MSI has been a biomarker associated with Lynch syndrome, the hereditary predisposition to colorectal and certain other cancers. In recent years, research interest in MSI has exploded, driven by the discovery that its presence in tumor tissue can be predictive of a positive response to anti-PD-1 immunotherapies (2,3).

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Five Fun Facts About Sloths and Three Things We Can Learn from Them

Sloths. These slow-moving, baby-faced, tree-dwelling mammals have risen to stardom in recent years, with their chubby, bandit-masked faces appearing on everything from socks and t-shirts to coffee mugs and post-it notes. We can all agree they are cute, but how much do we know about them?

Picture of a sloth hanging from a branch. Sloths are tree dwelling mammals.
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New Cleared IVD Assay for Microsatellite Instability in Colorectal Cancer Aims to Help Identify Those with Lynch Syndrome

Lynch syndrome is an inherited condition that significantly increases the risk of developing colorectal and other cancers, often at a young age. People with this condition have close to an 80% chance of developing colorectal cancer in their lifetime. It is the most common form of hereditary colon cancer and causes roughly 3% of all colon cancers. The mutations that cause Lynch syndrome are inherited in an autosomal dominant manner— ­meaning you only need to have one copy of the gene with a Lynch-associated mutation to be at an increased risk.

It is estimated that 1 in every 279 people have inherited a Lynch-associated mutation (1). Yet despite this prevelence, Lynch syndrome is not well known and ~95% of those with the syndrome don’t know they have it (1).

Lynch Syndrome Cause and Detection

Lynch syndrome is caused by mutations that result in the loss of function of one of the four different major mismatch repair proteins. These proteins act as “proof readers” that correct errors in the DNA sequence that can occur during DNA replication. To determine if Lynch syndrome is likely, simple screening tests can be performed on tumor (cancer) tissue to indicate if more specific genetic testing should be considered. One such screening looks for high levels of microsatellite instability (MSI) in the tumor tissue. High microsatellite instability (MSI-H) in tumor tissue is a functional indication that one or more of the major mismatch repair proteins is not functioning properly.

Watch this short video to learn more about microsatellite instability.

For those who develop colorectal cancer at an early age or have a family history (immediate family member or multiple family members with colorectal cancer or polyps), screening for Lynch syndrome can offer valuable insight for both patients and their family, as well as for their healthcare provider.

New MSI IVD Test for Colorectal Cancer to Help Identify Lynch Syndrome

The newly released Promega OncoMate™ MSI Dx Analysis System is an FDA-cleared IVD Medical Device and can be used to determine the MSI status of colorectal cancer tumors to aid in identifying those who should be further tested for Lynch syndrome. The OncoMate™ MSI Dx Analysis System builds upon the company’s fifteen year history of supporting global cancer researchers with one of the leading standard tests for MSI status detection. The OncoMate™ MSI Dx Analysis System offers an improved formulation while using the same five markers that have become the gold standard for MSI detection in the research community and is referenced in over 140 peer review publications (2,3).

The OncoMate™ MSI Dx Analysis System is designed to provide physicians with a functional, molecular measurement of the level of DNA mismatch repair deficiency demonstrated within their patient’s colorectal cancer tumor. MSI testing is recommended to identify candidates for further diagnostic testing for Lynch syndrome. (2–4). The System is part of a broader workflow that includes DNA extraction from FFPE tissue samples, quantitation of DNA, amplification of specific microsatellite markers using multiplex PCR, fragment separation by capillary electrophoresis, and data analysis and interpretation software. The OncoMate™ MSI Dx Analysis System is available in certain countries.  Visit the OncoMate™ MSI Dx Analysis System webpage to learn more.

Promega previously announced a CE-marked version of the OncoMate™ MSI  Dx Analysis System in France, Germany, Austria, Poland, UK, Ireland, Belgium, Netherlands, Luxembourg, Spain, Italy, Switzerland, Denmark, Sweden and Norway.

For more information about MSI solutions available from Promega visit our Microsatellite Instability Testing webpage.

References

  1. Win, A. K. et al. (2017) Cancer Epidemiol. Prev. 26, 404–12.
  2. Bacher, J. et al. (2004) Dis. Markers 20, 237–50.
  3. Svrek, M. et al. (2019) Bull. Cancer, 106, 119–28.
  4. Umar, A. et al. (2004) J. Natl. Cancer Inst. 18, 261–8.

Questions Arise about TMB as a Predictive Biomarker for Immune Checkpoint Inhibitor Therapy

Artist rendition of immune cells attacking a cancer cells. Immune checkpoint inhbitor therapy is a relatively new therapy for certain cancers.

Immune checkpoint inhibitor (ICI), or immune checkpoint blockade, therapies are a revolutionary, and relatively new, approach to treating cancer. These therapies work by blocking immune checkpoint proteins that act to negatively regulate the immune system through the PD-1 pathway. Some tumors express immune checkpoints to prevent the immune system from producing a strong enough immune response to kill the cancer cells. When these checkpoint proteins are blocked by an ICI, the body’s T-cells can recognize and kill the cancer cells. ICI therapies show tremendous promise. Unfortunately, not all tumors express immune checkpoint proteins, and so, not all tumors will be effectively treated with ICI therapies. The challenge is differentiating between the tumors that will respond and tumors that won’t.

DNA Mismatch Repair Deficiency Status as Detected by Microsatellite Instability or Immunohisotchemistry are Important Biomarkers for ICI

Biomarkers are measurable indicators of a clinical condition that can be found in tissue, blood, or other fluids. Predictive biomarkers for ICIs can help determine if these therapies are a suitable choice for treatment. Some tumors have deficiencies in their DNA mismatch repair mechanisms. Mismatch repair deficiency (dMMR) leads to the accumulation of mutations across the genome, particularly in microsatellites, which over time can result in higher levels of neoantigen production, rendering the tumors susceptible to the ICI therapy (1–5).

In 2017, Le et al. demonstrated that dMMR status reliably predicted response to an ICI therapy targeting the PD-1 checkpoint protein (6). Following this discovery, ICI based on dMMR  determined using either microsatellite instbility (MSI) or immunohistochemistry (IHC), gained clearance from the US Food and Drug Administation (FDA) for microsatellite instability-high (MSI-H) or dMMR by IHC solid tumors. This was the first time a cancer treatment was cleared based on a biomarker regardless of cancer origin (1,7).  Since then, MSI-H and dMMR, have become some of the most recognized tissue agnostic biomarkers for improved survival following ICI therapy of solid tumors (6,8,9).

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There’s a Vaccine for That—Could mRNA Vaccines be Used to Prevent Cancer Recurrence?

mRNA vaccines came roaring onto the public stage in 2020. In the United States and Europe, two of the vaccines that are being used against the SARS-CoV-2 virus are mRNA vaccines. The scientific community has been talking about the potential of this technology against infectious diseases as well as cancer for several years, but no one thought that the first mRNA vaccines would make such a huge, and public, debut.

One big benefit of mRNA vaccines is the speed at which they can be developed. mRNA vaccines use messenger RNA particles to teach our cells to make a bit of protein, which then triggers our body’s immune response, and it is relatively easy to synthesize large amounts of mRNA in a laboratory. As promising as this sounds for infectious diseases, the application of mRNA vaccines for oncology might be even more exciting.

Could mRNA vaccines be used for personalized cancer vaccines?
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Impact of COVID-19 Pandemic on Cancer Diagnosis—When Fewer Cases of Cancer is Not Good News

The year 2020 was a year filled with things we didn’t do. The global COVID-19 pandemic meant we didn’t gather with family and friends; we didn’t attend concerts or sporting events; we didn’t even go to work or school in the same way. We also didn’t go to the doctor, and as a result, many countries and organizations are reporting that there was an alarming drop in the number of new cancer cases (1–6). Unfortunately, while fewer diagnosis might sound like a good thing, there is no evidence that the actual rate of new cancer occurrence is declining (7).  

COVID-19 Restrictions Impact Cancer Screening and Diagnosis

The drop in cancer diagnosis happened after countries began to put into place new restrictions intended to slow the spread of the SARS-CoV-2 virus. These measures often included limiting or pausing many routine screenings and doctor visits, which also limited or paused opportunities to diagnosis cancer. The resulting decline in new cancer diagnosis was dramatic. In the United States, there was a 46.4% decline in the number of newly diagnosed cases of six of the most common cancer types (breast, colorectal, esophageal, gastric, lung and pancreatic) per week between March 1, 2020 and April 18, 2020 (1,2,8).

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Your Brain on COVID-19: Neurotropic Properties of the SARS-CoV-2 Virus

Updated 4/29/2022 by AnnaKay Kruger

Artist conception of coronavirus in the brain. Researchers are investigating the neurotropic effects of SARS-CoV-2

Viruses are both fascinating and terrifying. Stealthy, insidious and often deadly, they turn our own cells against us. Over the past year, we have all had a firsthand view of what a new and unknown virus can do. The SARS-CoV-2 virus has caused a global pandemic, and left scientists and medical professionals scrambling to unravel its mysteries and find ways to stop it.

COVID-19 is considered a respiratory disease, but we know that the SARS-CoV-2 virus can affect other systems in the body including the vascular and central nervous systems. In fact, some of the most noted symptoms of SARS-CoV-2 infection, headache, and the loss of the sense of taste and smell, are neurological— not respiratory— symptoms.

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