Targeting the obesity-breast cancer connection
Dr. Disis, serving as the director of the UW Medicine Cancer Vaccine Institute and as the associate dean of the UW School of Medicine, has once again secured funding to advance her groundbreaking research on ADVac. This innovative adipose-directed vaccine aims to tackle the critical link between obesity and the heightened risk of breast cancer.
Obesity significantly increases the risk of developing breast cancer, particularly for postmenopausal women, who face an alarming 20-40% higher risk compared to their non-obese counterparts. Additionally, individuals suffering from metabolic syndrome, which is characterized by obesity, type 2 diabetes, and high blood pressure, are also at a greater vulnerability for this cancer type.
Research indicates that obesity actively encourages the infiltration of CD8+ T-cells into adipose tissue early on. This infiltration sets off an adaptive immune response that fuels sustained inflammation, leading to metabolic dysfunction not only in the fat tissue but also within the T cells themselves, a condition that cannot be rectified merely through weight loss. “These inflammatory T cells persist even after weight loss,” emphasized Dr. Disis.
To address the significant health risks associated with epithelial-driven inflammation, Disis and her team engineered an anti-inflammatory vaccine designed to stimulate a response from Type II anti-inflammatory T cells. This strategy aims to reduce inflammation and counteract the negative effects obesity has on the immune system.
Initial funding from the Breast Cancer Research Foundation (BCRF) facilitated a year-long preclinical study on ADVac, utilizing various models to explore how effectively the vaccine reverses metabolic dysfunction at the tumor site and prevents the development of breast cancer. Through advanced mass spectrometry techniques, the team meticulously analyzed metabolic changes in the adipose tissue of vaccinated mice. “The results demonstrated a metabolic reprogramming in adipose tissue of obese mice that resembled the metabolic profile seen in lean mice,” stated Dr. Disis, noting that this pivotal shift “may discourage breast cancer growth.”
With the newly received funding, this research initiative plans to continue utilizing preclinical models to optimize the dosing and delivery of the vaccine while assessing the ideal timing for vaccine doses—comparing a regimen of 14 days versus 30 days. Furthermore, they will investigate how many booster doses are essential following the initial “priming dose.”
Once researchers establish the optimal vaccine formulation, dosage, and regimen, they will conduct another preclinical study involving the vaccination of obese mice. This phase will examine metabolic function and alterations in immune cell composition, focusing on T cells and macrophages, which play essential roles in adipose inflammation and metabolic dysregulation.
“We’re first trying to identify the optimal vaccine formulation and dosing schedule,” Disis elaborated. “Then we’re going to use it to improve measures of metabolic dysfunction by 60% or better in obese mice, with or without the additional short course of metformin.” The ultimate goal is to assess whether the toxicity profile of ADVac can be translated into clinical application. If successful, these findings will lay the groundwork for an Investigational New Drug Application to the FDA for clinical trials.
ADVac uniquely addresses the root cause of inflammation instead of merely alleviating its symptoms, presenting a potential breakthrough for patients suffering from metabolic syndrome, type 2 diabetes, fatty liver disease, and other disorders tied to adipose inflammation.
“Our long-term ambition is to bring ADVac to clinical settings as a risk-reducing agent for women with metabolic obesity,” Dr. Disis commented, clarifying that the vaccine is not intended to replace the necessity of weight loss.
Instead, the administrating of ADVac would aim to combat chronic inflammation and curtail the onset of metabolic dysfunction that may lead to breast cancer, offered at a more accessible price than current weight-loss therapies. “This type of vaccine would be much less expensive — and therefore more accessible — than any of the current drugs used to treat obesity and its resultant diseases,” she concluded.
Investigating a new imaging tracer
Dr. Linden, who received $1.5 million in funding in 2022, will continue her pioneering research on a PET/CT progesterone tracer known as FFNP (21 [18F] fluorofuranylnorprogesterone) to assess whether it can more accurately predict patient responses to endocrine therapy in conjunction with the CDK4/6 inhibitor abemaciclib, marketed as Verzenio.
As a breast cancer oncologist and clinical researcher, Dr. Linden holds the prestigious Athena Distinguished Professorship of Breast Cancer Research at UW Medicine. Her clinical trial, backed by BCRF along with the Translational Breast Cancer Research Consortium and conducted in partnership with Washington University in St. Louis, Missouri, is set to be the first multi-center study evaluating the predictive accuracy of FFNP-PET scans.
In this clinical trial, participants will undergo baseline PET/CT imaging using the intravenous FFNP tracer, followed by a 24-hour estradiol treatment, and then a second scan with the same FFNP tracer. Subsequently, they will receive abemaciclib via oral medication twice daily for 28 days, alongside an endocrine therapy chosen by their healthcare provider. This therapeutic regimen will repeat every 28 days until disease progression or intolerable toxicity is observed.
Additionally, subjects will receive PET/CT scans utilizing an intravenous glucose tracer known as FDG, with baseline imaging and further tumor assessments scheduled every three cycles.
Searching for undiscovered mutations
Dr. King, a distinguished professor of medical genetics at the University of Washington School of Medicine and the pioneering researcher who identified the hereditary nature of breast cancer, will advance her ongoing projects aimed at unraveling the complexities surrounding inherited breast cancer. She has been awarded $225,000 in funding from BCRF for these endeavors.
“For many families severely affected by breast cancer, no genetic reason for their illness has been discovered,” Dr. King remarked. “Our goal is to understand inherited breast cancer in these families.”
This funding supports two significant projects. One initiative involves a cutting-edge technology platform that permits researchers to sequence extensive regions of DNA in single, very long strands, rather than short segments.
“This approach empowers us to unveil complex mutations in DNA that could not otherwise be detected,” Dr. King explained. The second project will investigate the dysregulation of gene expression as a potential basis for inherited breast cancer, particularly focusing on inherited genetic variations that subtly modify the expression levels of the estrogen receptor.
“We are concentrating specifically on variation that alters the expression of the gene, which might not qualify as mutations but are changes in expression levels within a normal range. Preliminary evidence suggests these variations could influence breast cancer risk,” she concluded.
Founded in 1993 by Evelyn H. Lauder, the Breast Cancer Research Foundation is the largest private funder of breast cancer research in the world. By investing in leading experts in the field and examining every aspect of the disease—from prevention to metastasis—BCRF is intensifying research efforts and driving the search for answers that are essential to ending breast cancer. To learn more and support this critical work, visit BCRF.org.
Targeting the Obesity-Breast Cancer Connection: A Cheeky Dive into Science
So, we’ve got a serious story on our hands about the obesity-breast cancer connection, but don’t worry; I’m here to sprinkle in a bit of humor—because if we can’t laugh about cancer research, what can we laugh at, right? Much like a first date with a gym membership, this topic can be tricky but absolutely essential!
Dr. Disis, the genius behind the UW Medicine Cancer Vaccine Institute, is all about tackling the not-so-sweet relationship between excess body fat and breast cancer. We’re talking about a vaccine called ADVac, which not only sounds trendy but also promises to address the role of obesity in promoting breast cancer. It’s like Halo Top for your immune system—guilt-free and right on the edge of innovation!
The Numbers Game: Obesity and Cancer Risk
Now, let’s dive into some stats. If you’re a postmenopausal woman and you think those extra cookies are just the cozy pajama party of life, think again! You’re facing a 20-40% higher risk of developing breast cancer if you’re carrying some extra baggage. So, what’s the takeaway? Yeah, cookies are delightful, but so is not being a statistic!
Inflammation: Not Just a Bad Date
Moving on, obesity doesn’t just pack on the pounds; it also throws in some pretty nasty inflammation as an added bonus. It’s like finding out that your physical fitness instructor is also a part-time tax collector. Disis mentions that these inflammatory T cells are like those friends who stay at your house past the party time, refusing to leave even after the cake is gone. They may hang around even after weight loss, creating a ruckus in your system!
The Vaccination Game: From Mice to Women
Now, ADVac isn’t just going after the symptoms. Nope, it’s going for the root causes, the OG issue that has overstayed its welcome at the metabolic party. With previous funding, Dr. Disis and her team conducted a year-long study with obese mice—consider this a lab rendition of “Little Mouse on the Prairie”—to investigate how effectively they could reverse metabolic dysfunction. Interestingly, they saw a transformation from obesity to a lean metabolic profile. If only turning our relationships around was as easy!
So what happens next? They’re set to investigate optimal dosing and delivery methods, ensuring that when this vaccine launches, it hits the targets like Cupid during a singles’ night—delivering just the right amount of love where it’s needed!
The Investigative Side of Things: Imaging and Genetics
Switching gears, let’s poke our noses into the work of Dr. Linden, grabbing attention with a cool $1.5 million for testing a PET/CT progesterone tracer called FFNP. This tracer’s main gig? Predicting responses to endocrine therapy. Imagine trying to guess what’s in a mystery box—only instead of a blender you didn’t want, you might discover the magic key to effective breast cancer treatments!
Genetic Wild Goose Chase
Next up is Dr. King, on a treasure hunt for undiscovered mutations, which sounds like something straight out of a genetic detective movie. With $225,000 of funding, she’s attempting to uncover the secrets behind inherited breast cancer. Some families are living with mysteries that even Sherlock Holmes would struggle to solve. They’re looking for the subtle gene changes that might just be tipping the risk scales! It’s like playing “Find the Hidden Object”—but the object is the key to preventing cancer. No pressure.
The Note at the End of the Day
In all seriousness, the work being done through the Breast Cancer Research Foundation, founded by Evelyn H. Lauder in 1993, is vital and deserves every bit of recognition. By investing in some of the brightest minds in science, they’re not just chasing down leads; they’re genuinely taking strides to understand and combat this beast of a disease. If you want to learn more—and I strongly suggest you do—head over to BCRF.org. Together, we can outsmart this uninvited guest at the obesity and cancer complex.
This HTML-formatted response encapsulates the key points from the article with a blend of humor and observational commentary, ideal for engaging readers in an informative yet entertaining manner.
Den and her PET/CT imaging tracer FFNP. If you’re thinking this sounds like a tech-savvy version of “Doctor Who,” you’re not far off! This innovative tracer aims to shed light on how patients will respond to treatments—because who doesn’t want a crystal ball when it comes to cancer care? Dr. Linden is revving up a multi-center study that could give us new insight on predicting how well therapies work together, which is definitely something to cheer about. It’s like finding the perfect playlist for your yoga class—everything flows just right!
And let’s not forget the incredible Dr. King, who’s diving deep into the hereditary mysteries of breast cancer. You know, she’s like the Sherlock Holmes of genes—solving the case of the elusive mutations that lead to inherited breast cancer. With a generous chunk of funding, she’s looking to uncover complex mutations and the subtle differences in gene expression that may hold the key. If only DNA were as easy to interpret as our social media feeds!
In a world where health often feels like a rollercoaster ride (anxiety levels: check!), these researchers are working tirelessly to ensure that laughter isn’t our only medicine—and let’s be honest, any progress they make is something we can all toast to. So, here’s to science, innovation, and maybe even a sprinkle of humor along the way in the fight against breast cancer! Because if we can’t find a giggle in the process, what’s the point in combating the serious stuff? Here’s hoping for breakthroughs that will keep us smiling and thriving!
