In the field of cancer research, accurately measuring cell proliferation is crucial for assessing the efficacy of therapeutic agents. This is particularly difficult with CDK 4/6 inhibitors, which arrest cells in the G1 phase without stopping their growth. This continued growth can skew results from proliferation assays which rely on factors that naturally scale with cell growth. These include mitochondrial activity (ATP levels), total cell protein, or mRNA as measured through the PRISM molecular barcoding strategy. Even though these cells are not dividing, the increase in these measurements can misleadingly suggest active proliferation.
There is growing awareness among researchers of these challenges. A recent study highlights these limitations by demonstrating the discrepancies that arise when using metabolic assays to assess cell proliferation after treatment with drugs that induce cell cycle arrest. This blog post delves into the study’s implications and demonstrates how one of Promega’s latest developments is poised to address these challenges.
Nicotinamide adenine dinucleotide (NAD) exists in two forms in the cell: NAD+ (oxidized) and NADH (reduced). This molecule plays a pivotal role in metabolic processes, serving as a key electron carrier in the redox reactions that drive cellular metabolism. The balance between these two forms, commonly expressed as the NAD+/NADH ratio, is crucial for maintaining cellular function and the intracellular redox state. This article explores the significance of this ratio, how it impacts cellular processes, and the consequences of NAD+/NADH ratio dysregulation.
Discovered in 1983 and initially dismissed as ‘cellular dust,’ exosomes have since emerged as pivotal players in biomedical research due to their roles in intercellular communication, potential as drug delivery vectors and as biomarkers for various diseases. These small extracellular vesicles, measuring 30–150nm, are crucial for transferring proteins, lipids, and nucleic acids — including microRNA (miRNA), mRNA, and non-coding RNA– between cells (1). miRNAs are particularly critical as they regulate gene expression and offer insights into the cellular mechanisms underlying diseases like cancer, enhancing the value of exosomes in cancer research.
Beyond exosomes importance in understanding intracellular communication and organ cross-talk, exosomes can also alter the functions of recipient cells based on their cargo. This capability makes them extremely valuable in providing insights into alterations in cellular communication, tumor microenvironments, metastasis and immune evasion.
At the American Association for Cancer Research meeting in April 2016, then Vice President of the United States, Joe Biden, revealed the Cancer Moonshot℠ initiative— a program with the goals of accelerating scientific discovery in cancer research, fostering greater collaboration among researchers, and improving the sharing of data (1,2). The Cancer Moonshot is part of the 21st Century Cures Act, which earmarked $1.8 billion for cancer-related initiatives over 7 years. The National Cancer Institute (NCI) and the Cancer Moonshot program have supported over 70 programs and consortia, and more than 250 research projects. According to the NCI, the initiative from 2017 to 2021 resulted in over 2,000 publications, 49 clinical trials and more than 30 patent filings. Additionally, the launch of trials.cancer.gov has made information about all cancer research trials accessible to anyone who needs it (3).
“We will build a future where the word ‘cancer’ loses its power.”
First Lady, Dr. Jill Biden
In February 2022, the Biden White House announced a plan to “supercharge the Cancer Moonshot as an essential effort of the Biden-Harris administration” (4). Biden noted in his address that, in the 25 years following the Nixon administration’s enactment of the National Cancer Act in 1971, significant strides were made in understanding cancer. It is now recognized not as a single disease, but as a collection comprising over 200 distinct diseases. This period also saw the development of new therapies and enhancements in diagnosis. However, despite a reduction in the cancer death rate by more than 25% over the past 25 years, cancer continues to be the second leading cause of death in the United States [4].
The Cancer Moonshot is a holistic attempt to improve access to information, support and patient experiences, while fostering the development of new therapeutics and research approaches to studying cancer. In this article, we will focus on research, diagnostics and drug discovery developments.
Solving for Undruggable Targets
KRAS , a member of the RAS family, has long been described as “undruggable” in large part because it is a small protein with a smooth surface that does not present many places for small molecule drugs to bind. The KRAS protein acts like an off/on switch depending upon whether it has GDP or GTP bound. KRAS mutations are associated with many cancers including colorectal cancer (CRC), non-small cell lung cancer (NSCLC), and pancreatic ductal adenocarcinoma (PDAC). The G12 position in the protein is the most commonly mutated; G12C accounts for 13% of the mutations at this site, and is the predominant substitution found in NSCLC, while G12D is prevalent in PDAC (5).
In January 2024, Antonio Alcamí and Ángela Vázquez, virologists from the Severo Ochoa Centre for Molecular Biology, landed in Antarctica to study the avian flu virus. They embarked on a journey to monitor 17,000 penguins as part of their efforts to study the virus and prevent its spread. Our Maxwell® RSC 48 was delivered to extract nucleic acids from the samples, which are set to be analyzed using qPCR.
This blog is guest-written by Jason Hankes, Manager, Land & Natural Resources, Promega Corporation
At Promega, the arrival of spring is not merely a celebration of nature’s rejuvenation, but also a reflection of our steadfast commitment to environmental stewardship. This vibrant season allows us to spotlight a crucial ecological initiative: the controlled prairie burn. Conducted every three to five years across over 25 acres of native prairie restorations, these burns are essential for habitat health. They not only reduce the risk of wildfires but also curb invasive weeds and stimulate new growth. Undertaking these burns exemplifies how Promega reinforces its commitment to environmental stewardship – a foundational principle that guides our operations and influences our architectural designs.
This guest blog post is written by Tara Luther, Sr. Marketing Specialist, Genetic Identityat Promega.
April 2024 marked the 23rd anniversary of Sexual Assault Awareness Month (SAAM) in the United States. While we have crossed into May, the importance of what SAAM stands for does not diminish with the changing of the calendar. The National Sexual Violence Resource Center (NSVRC) emphasizes that SAAM is a time to not only draw attention to the prevalence of sexual assault, but to also educate individuals and communities about how to prevent sexual violence.
An amazing transformation is taking place, unseen and unnoticed, within the microscopic bits that make you, you.
A tightly coiled lattice unspools to reveal a sinuous DNA stand. Along its length, tendrils of RNA sprout, growing bit by genetic bit. Eventually, the signal to stop and break away arrives, yielding a new strand of RNA that faithfully transcribes the DNA strand’s genetic code. Proteins trim and splice this new growth, pruning it so it takes its final form, messenger RNA. More proteins then ferry this mRNA strand through a pore in the nuclear envelope into the open space of the cell’s cytoplasm. Ribosomes and codon-carrying tRNA alight onto the released mRNA strand, reading the instructions it has carried from the DNA in the nuclear nursery. From this trio new forms emerge, bulbous proteins shaped by their destined purpose.
And so it goes, every second of every day, in the tens of trillions of cells in your body…
…And on the tens of thousands of kit packages we deliver to customers across the globe every year.
On April 21st, 2024, hundreds of volunteers accompanied four local artists in Madison, Wisconsin for a public painting event to help decorate the 400-600 blocks of State Street. This project is the first embodiment of the city of Madison’s pedestrian mall experiment, set to kick off in May. Taylor McAda, Promega Senior Graphic Designer, was selected to design and paint one of four original 20-foot circle murals.
For decades, pharmaceutical companies have relied on high-throughput screening (HTS) as the first step in the drug discovery process. After an initial screening of thousands of compounds, scientists select a smaller list of candidate drugs that is then used for further downstream testing. A major limitation to HTS, however, is the need to synthesize all compounds used in the screen—the compounds need to physically exist to be tested. This significantly limits the number of compounds that can be tested, hindering the discovery of new drugs.
What if we could test compounds even before they are synthesized?
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