Author: Kelly Grooms

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

Posted on by Kelly Grooms
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).

Continue reading “Questions Arise about TMB as a Predictive Biomarker for Immune Checkpoint Inhibitor Therapy”

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

Posted on by Kelly Grooms

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

Impact of COVID-19 Pandemic on Cancer Diagnosis—When Fewer Cases of Cancer is Not Good News

Posted on by Kelly Grooms

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).

Continue reading “Impact of COVID-19 Pandemic on Cancer Diagnosis—When Fewer Cases of Cancer is Not Good News”

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

Posted on by Kelly Grooms

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.

Continue reading “Your Brain on COVID-19: Neurotropic Properties of the SARS-CoV-2 Virus”

Increasing Testing Efficiency with Multiplexed Detection of SARS-CoV-2 and Influenza A and B

Posted on by Kelly Grooms

In the Northern hemisphere, the cold and flu season is about to start. Most years that means people schedule flu shots, dust off chicken soup recipes and stock up on tissues. If they start to feel sick, they stay home for a day or two, drink hot tea, eat warm soup and—for the most part— go on with their lives. 

This is not, however, most years. This year the world is battling a pandemic virus, SARS-CoV-2. Symptoms of COVID-19, the disease caused by this virus, mirror those of the flu and common cold, and that overlap in symptoms is going to make life more complicated. Most years, a mild cough or minor body aches wouldn’t even warrant a call to the doctor. This year these, and other undiagnosed cold- and flu-like symptoms, won’t be easily ignored. They could mean kids have to stay home from school, and adults have to self-quarantine from work, for up to 2 weeks. In years past people might have been comfortable treating their symptoms at home, this year people will want answers: Is it the flu? Or is it COVID-19?

Continue reading “Increasing Testing Efficiency with Multiplexed Detection of SARS-CoV-2 and Influenza A and B”

Lessons in History, Hope and Living with Lynch Syndrome from the “Daughter of Family G”

Posted on by Kelly Grooms

Lynch Syndrome is the autosomal dominant hereditary predisposition to develop colorectal cancer and certain other cancers. This simple, one sentence definition seems woefully inadequate considering the human toll this condition has inflicted on the families that have it in their genetic pedigree.

They Called it a Curse

To one family, perhaps the family when it comes to this condition, Lynch Syndrome has meant heartache and hope; grief and joy; death and life. Their story is told by Ami McKay in her book Daughter of Family G, and it is at once both a memoir of a Lynch Syndrome previvor (someone with a Lynch Syndrome genomic mutation who has not yet developed cancer) and a poignant and honest account of the family that helped science put name to a curse.

“The doctors called it cancer. I say it’s a curse. I wish I knew what we did to deserve it.”

Anna Haab from Daughter of Family G (1)

The scientific community first met “Family G” as the meticulously created family tree, filled with the stunted branches that mark early deaths by cancer. The pedigree was first published in 1913 in Archives of Internal Medicine (2). In the article, Dr. Alderd Warthin wrote: “A marked susceptibility to carcinoma exists in the case of certain family generations and family groups.” In 1925, an expanded pedigree of circles and squares was published in Dr. Warthin’s follow up study in the Journal of Cancer Research (3).  But each circle and square in that pedigree denotes a person. Each line represents their dreams together for the future, and Ms. McKay wants us to know their names: Johannes and Anna, Kathrina, Elmer, Tillie, Sarah Anne (Sally); and—most importantly—Pauline. Because without Pauline there would be no story.

Continue reading “Lessons in History, Hope and Living with Lynch Syndrome from the “Daughter of Family G””

Promega Leverages Long-Time Experience in MSI Detection with European Launch of CE-Marked IVD Assay for Microsatellite Instability

Posted on by Kelly Grooms

The genetic abnormality called microsatellite instability, or MSI, has been linked to cancer since its discovery in 1993 (1). MSI is the accumulation of insertion or deletion errors at microsatellite repeat sequences in cancer cells and results from a functional deficiency within one or more major DNA mismatch repair proteins (dMMR).  This deficiency, and the resulting genetic instability, is closely related to the carcinogenicity of tumors (2).

Historically MSI has been used to screen for Lynch Syndrome, a dominant hereditary cancer propensity. More recently, tumors with deficient MMR function have been identified as being more likely to respond to immune checkpoint inhibitor (ICI) therapies (3.). Because MSI can be the first evidence of an MMR deficiency, MSI-High status is predictive of a positive response to immunotherapies such as ICI therapies. (3).

Learn more about MSI in this short animation.
Continue reading “Promega Leverages Long-Time Experience in MSI Detection with European Launch of CE-Marked IVD Assay for Microsatellite Instability”

RT-qPCR and qPCR Assays—Detecting Viruses and Beyond

Posted on by Kelly Grooms

We have all been hearing a lot about RT-PCR, rRT-PCR and RT-qPCR lately, and for good reason. Real-Time Reverse Transcriptase Polymerase Chain Reaction (rRT-PCR) is the technique used in by the Center for Disease Control (CDC) to test for COVID-19. Real-time RT-PCR, or quantitative RT-PCR (RT-qPCR)*, is a specialized PCR technique that visualizes the amplification of the target sequence as it happens (in real-time) and allows you to measure the amount of starting target material in your reaction. You can read more about the basics of this technique, and watch a webinar here. For more about RT-PCR for COVID-19 testing, read this blog.

Both qPCR and RT-qPCR are powerful tools for scientists to have at their disposal. These fundamental techniques are used to study biological processes in a wide range of areas. Over the decades, Promega has supported researchers with RT-qPCR and qPCR reagents and systems to study everything from diseases like COVID-19 and cancer to viruses in elephants and the circadian rhythm of krill.  

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Optimizing PCR: One Scientist’s Not So Fond Memories

Posted on by Kelly Grooms

primer_tubesThe first time I performed PCR was in 1992. I was finishing my Bachelors in Genetics and had an independent study project in a population genetics laboratory. My task was to try using a new technique, RAPD PCR, to distinguish clonal populations of the sea anemone, Metridium senile. These creatures can reproduce both sexually and asexually, which can make population genetics studies challenging. My professor was looking for a relatively simple method to identify individuals who were genetically identical (i.e., potential clones).

PCR was still in its infancy. No one in my lab had ever tried it before, and the department had one thermal cycler, which was located in a building across the street. We had a paper describing RAPD PCR for population work, so we ordered primers and Taq DNA polymerase and set about grinding up bits of frozen sea anemone to isolate the DNA. [The grinding process had to be done using a mortar and pestle seated in a bath of liquid nitrogen because the tissue had to remain frozen. If it thawed it became a disgusting mass of goo that was useless—but that is a topic for a different blog.] Since I had never done any of the procedures before, my professor and I assembled the first set of reactions together. When we ran our results on a gel, we had all sorts of bands—just what he was hoping to see. Unfortunately, we realized that we had added 10X more Taq DNA polymerase than we should have used. I repeated the amplification with the correct amount of Taq polymerase, and I saw nothing. Continue reading “Optimizing PCR: One Scientist’s Not So Fond Memories”

Selecting the Right Colony: The Answer is There in Blue and White

Posted on by Kelly Grooms
Agar plate containing colonies important for research, blue and white.
Agar plate containing colonies important for research.

Ah, the wonders and frustrations of cloning. We’ve all been there. After careful planning, you have created the cloned plasmid containing your DNA sequence of interest, transformed it into bacterial cells and carefully spread those cells on a plate to grow. Now you stand at your bench gazing down at your master piece: a plate full of tiny bacterial colonies. Somewhere inside those cells is your DNA sequence, happily replicating with its plasmid host. But wait – logic tells you that not ALL of those colonies can contain your plasmid.  There must be hundreds of colonies. Which ones have your plasmid? You begin to panic. Visions of yourself old and grey and still screening colonies flash through your mind. At the next bench, your lab-mate is cheerfully selecting colonies to screen. Although there are hundreds of colonies on her plate as well, some are white and some are blue. She is only picking the white colonies. What does she know that you don’t?

Continue reading “Selecting the Right Colony: The Answer is There in Blue and White”