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A promising fatty liver treatment may raise cancer risk
A surprising new study reveals that blocking a supposedly protective enzyme, Caspase-2, could actually backfire—raising the risk of chronic liver damage and cancer over time. Researchers found that without this enzyme, liver cells grow abnormally large and accumulate genetic damage, leading to inflammation, scarring, and eventually tumors, especially with age. While inhibiting Caspase-2 may offer short-term benefits, such as reducing fatty liver disease, the long-term consequences appear dangerous.
Your Thymus and Your Healthspan
Our thymus gland plays a central role in the development or our immune system, specifically for supporting T cell development (how these cells got their name, maturation and differentiation in the thymus) and discriminating between self and foreign, non-self antigen proteins with production of dendritic cells. As we age, our thymus gland shrinks—the process known as involution—with progressive change from spongy to fatty tissue, with loss of functionality. But this process, with respect to timeline and extent, markedly varies from one person to the next. And to make things even more complicated, our thymus gland anatomy and precise location in the chest also is highly variable. So the famous Frank Netter diagrams from the 1960s (such as at left below) don’t capture the remarkable heterogeneity that a random set of 12 chest CT scans (below at right). What I consider as 2 landmark papers in Nature this week (here and here) used AI to quantify health of the thymus in 2 large cohorts, and then correlate the metric to a broad array of health outcomes. In this edition of Ground Truths, I’m going to cover three questions: (1) How was thymus health determined by AI?; (2) How is thymus health linked to key clinical outcomes? and (3) Are there ways we can promote a healthy (aka rejuvenate) thymus gland in our later years? Subscribe 1. How was thymus health determined by AI? This was accomplished by extensive work developing and validating an AI pipeline for 2 stages, the first for localization and segmentation of the thymus bed, and the second to quantify a digital marker, termed the thymic health score. There’s a lot to this algorithmic development, so I won’t go into all the details, but just provide a rudimentary outline of what was done. The 1st stage used supervised learning with 2 radiologists reviewing 2,461 chest CT scans. That work trained a 3D U-Net model to automatically identify the thymic bed’s 3D cropped region using center of mass coordinates, which reached 99.8% accuracy. The 2nd stage used a foundation model that was pre-trained with SwAV (which stands for Swapping Assignment between multiple Views), a self-supervised model, that generated a high-dimensional thymus representation of 4,096 features. That compares to the radiology reductionist and subjective scoring of 0 to 3 where 0 means the thymus is fully degenerated and fatty, and 3 is considered dense, intact glandular soft tissue. Notably, the self-supervised learning (SSL) performance was superior to supervised (AUC ~0.75 vs 0.55, respectively) reflecting the shallowness of the 0-3 classifier vs SSL’s holistic, self-taught AI. The thymic health score ranged from 0 to 100, with the highest number indexed to fully preserved thymic health. The algorithmic work extended to explainability with both Shapely value distribution, meaning the model was holistic not relying on any “magic” pixel, and occlusion sensitivity, demonstrating the model’s performance was not affected by ribs, sternum, lung tissue, but rather focused on the thymic bed directly. Below are a few saliency maps from the occlusion sensitivity that indicate the thymic bed focus, not affected by neighboring structures, using the jet color scale. Now the AI was ready for processing ~25,000 CT scans, each over 30 MB files, from the 2 large participant cohorts to provide a thymic health score, it did so in less than 14 hours, which is less than 2 seconds per scan! Share 2. How is thymus health linked to key clinical outcomes? The two cohorts were the National Lung Screening Trial, NLST (N=25,031) and the Framingham Heart Study, FHS (N=2,581) each with baseline demographics and long term follow up of >12 years for health outcomes. From the NSLT, you can see below that increased age and body-mass index were correlated to reduced thymic health. And, overall, men had reduced thymic health scores compared with women. There are a lot of graphs in the paper for outcomes, for both the NLST and FHS cohorts. To simplify the major outcomes, below is a composite Figure with striking reduction of all-cause mortality and for the different causes of death. The results were consistent between the 2 cohorts. For example, the cardiovascular mortality hazard ratio average was 0.57 in NLST and 0.38 in FHS (weighted to be 0.53 for the aggregate). The reduction of mortality also extended to digestive diseases and pulmonary disease (data not shown below). Lung cancer incidence was reduced by 36% for high vs low thymic health (Figure below, with a panel -incidence and b panel-mortality, adjusted for age, sex, BMI, smoking status). Notably, there was a smoker’s paradox: lower incidence and improved survival for lung cancer in smokers who had a high thymus health score. Smoking was associated with lower thymic scores whereas alcohol was not. Higher thymic health was linked to higher HDL cholesterol, lower triglycerides, lower fasting blood glucose, and lower systolic and diastolic blood pressure. Inflammation biomarkers, such as C-reactive protein and interleukin-6, were elevated in the people with lower thymic health scores. In their second paper, the same team looked at the relationship between thymic score and outcomes for 3,476 patients receiving cancer immunotherapy. The non-small cell lung cancer progression-free survival was reduced in patients with low thymic health score. A parallel relationship for survival was seen for other types of cancer including melanoma, breast, and kidney with a 44% lower risk among high thymic scores (Figure). A similar pattern was seen with different immune checkpoint inhibitors. The thymus health score outperformed programmed death ligand-1 (PD-L1)and tumor mutation burden (TMB) assay of the tumor and was an independent prognostic marker of progression-free survival. In this dataset, a direct connect with thymus score and adaptive immune function was noted with a correlation before cancer treatment for both T-cell diversity and thymus T-cell production (a metric known as T cell receptor excision circles). Thymus Removal Study There is a highly relevant citation about thymus function before moving onto ways to rejuvenate it. In 2023, a very important study of thymus removal during cardiothoracic surgery was published, with 1146 patients undergoing thymus removal vs 1146 matched controls (mean age 55 years). The adverse outcomes for thymus removal were striking, with a 2.9 higher risk of all-cause mortality and doubling of cancer incidence, 1.5 fold increase in cancer mortality, and 1.5-fold increase in autoimmune diseases. The immune function showed marked compromise after thymus removal, as reflected by CD4+ and CD8+ T cells (Figure below) Share Ground Truths 3. Are there ways we can promote a healthy (aka rejuvenate) thymus gland in our later years? In recent months we’ve learned a lot about the process of thymus involution and the pathways by which this may be modulated. Thymus involution is primarily due to loss to thymus epithelial cells (TECs) and there are 2 subtypes with different functions: the cortical, responsible for positive selection of T cells, and the medullary, for negative selection. When adipose tissue infiltrates the thymus, thymic adipocytes are pro-inflammatory, knocking out T-cell output. Likewise, systemic inflammation, or “inflammaging,” from smoking, obesity, and chronic stress promote thymic adipocytes. Now, from preclinical studies, we know about key pathways that account for these processes. Historically, back in 2014, FOXN1 was recognized as a single master transcription factor essential for TEC function, with studies in mice with forced FOXN1 upregulation leading to thymus regeneration. That laid the foundation for potential regrowth of quiescent thymus cells. It took awhile to find pathways to accomplish this goal and to even refute its role as the master regulator. The Liver-Thymus Axis Feng Zhang and his team recently showed that injection of an mRNA vaccine to the liver encoding DLL1, IL-7 and FLT3-L in combination, factors known to support thymopoiesis (Figure), successfully enhanced immune function in aged mice. However, the effect was transient. The FGF21 Story Two reports in 2025 addressed the thymus gland’s production of FGF21, a growth factor (fibroblast growth factor 21) and its control of thymus involution. This growth factor is also produced by the liver, but it doesn’t have impact on the thymus in aged rodent models. In contrast, The liver’s hepatocyte growth factor (HGF) has been shown to reverse senescent TEC structural changes. Growth hormone stimulates production of insulin growth factor-1 (IGF-1) in the liver and the thymus. Two small studies in human participants (TRIIM, for Thymus Regeneration, Immunorestoration, and Insulin Mitigation) of 6 and 50 people, respectively, treated with combined human growth hormone, metformin and DHEA, suggested the potential of slowing epigenetic aging and improving thymus mass and function. But the combination of drugs, small sample, and lack of controls make conclusions murky. Increased thymus FGF21 led to increased CD8 T cells in old mice and extended healthspan and improved physical performance. Building on the previous FOXN1 data, ablation of β-klotho, the obligatory co-receptor for FOXN1, accelerated thymic aging. The benefit to FGF21 was confirmed in a companion paper using an FGF21 knock-in mouse model showing thymus enlargement and increased TECs throughout the lifespan. (schematic Figure below). The accompanying editorial for these 2 papers speculated: “The proposed link between age-associated thymus involution and organismal aging is intriguing, and suggests we might seek to achieve systemic rejuvenation by counteracting thymic involution.” Other Factors Lessons from the Axolotl (Mexican Salamander) In an elegant set of experiments of the axolotl (Figure), known for its complete thymus regeneration after total surgical removal, mediators were identified. Surprisingly FOXN1 was dispensable. But midkine, a growth factor, appeared to be the driver, the initiator of thymus cell growth, survival, and repair. Other components that contributed were Postn+ (periostin-expressing mesenchymal niches) and Ccl19, a chemokine protein from the bloodstream. RANK and RANKL RANK (receptor activator of nuclear factor κB its ligand (RANKL) have been considered key regulators of medullary TECs. In a study of both aged mice and human thymus cell cultures, their key role was confirmed, with multiple benefits of resorting TEC function, recruitment of progenitor cells, and T cell development. Subscribe Summing Up This body of work strongly supports the health of the thymus gland as a critical regulator of human healthspan, not just a correlate or link. The new landmark studies are reinforced by the regenerative biology experimental models that have shown, via an array of mediators, that healthspan of aged mice is at least in part dependent on thymus gland function and its critical role for maintaining adaptive immunity. It sure seems that we’d be better off having an immune reservoir of naive T cells instead of a profile in older adults of exhausted, low quality, memory T cells, with a senescent phenotype. It is striking that we ignored the importance of the thymus gland for many decades. A wake-up call was the results of the thymectomy matched control study reviewed here, with the opposite of high thymic health score improved health outcomes. The convergence of AI and healthspan here is notable. The exceptional and laborious work for developing and validating (no less explaining) the AI to quantify thymus health set the foundation for probing the connect the major health outcomes in two cohorts with extensive follow-up. We’ve never had a way to meaningfully quantify the thymus gland before, so this represents important leverage of supervised, self-supervised, and transformer models. The study wouldn’t have been possible without AI. And it begs the question as to whether there are ways we can maintain our thymus at a high health score. But it’s not so simple to rejuvenate our thymus. There are multiple risks including the induction of autoimmunity, increasing the risk of cancer, and inducing a pro-inflammatory state. For example, factors that increase TEC proliferation could compromise the medulllary negative selection process and leak out auto-reactive (self-attacking) T cells. Thymic cells could be induced to proliferate, but we know, for example, that growth hormone and IGF-1 are associated with an increase risk of cancer. If thymus rejuvenation doesn’t clear out the accumulated senescent cells in older adults, then inflammation within the gland could block the production of TECs. Keeping these risks in mind, we now have identified many ways to keep our thymus healthy as we age that undoubtedly will be tested in clinical trials going forward. Ultimately, the benefit-to-risk tradeoffs will be defined. In the meantime, we have desperately needed an immunome. As I’ve stressed in multiple prior Ground Truths, we have no test in the clinic to assess a patient’s immune status! It was very encouraging for me to get an email from Hugo Aerts, the senior author of the landmark papers in the days after they were published: “I also wanted to say that your Substack on “Why We Need an Immunome” was inspiring for this work. We found it a very compelling perspective and greatly enjoyed reading it.” Just having an assessment of a person’s immune status via a chest CT scan, with millions of these performed per year, might help in guiding the right immunotherapy for cancer (e.g. more intensive, combinations for those with low thymic health scores) and help define people who are increased risk for age-related diseases of cancer, cardiovascular, and neurodegenerative. The main theme of Super Agers is that we now have many layers of data (genetics, proteins, biomarkers, organ clocks that can be integrated via multimodal AI) for us to define a person’s specific risk decades before one of these age-related diseases leads to symptoms, enabling prevention. From the new studies this week, we can add thymus health score as yet another way to understand a person’s risk, a window into their adaptive immune system and healthspan. And perhaps someday we will be able to safely rejuvenate the thymus, or maintain its health through one’s life, and use the thymus health score to monitor. NB: I wrote this post (No A.I.) A Quick Poll Loading... ********************************************************************* Thanks to Ground Truths subscribers (now > 200,000) from every US state and 212 countries. Your subscription to these free essays and podcasts makes my work in putting them together worthwhile. Please join! If you found this interesting PLEASE share it! Share Ground Truths Paid subscriptions are voluntary and all proceeds from them go to support Scripps Research. They do allow for posting comments and questions, which I do my best to respond to. Please don’t hesitate to post comments and give me feedback. Let me know topics that you would like to see covered. Leave a comment Many thanks to those who have contributed—they have greatly helped fund our summer internship programs for the past two years. It enabled us to accept and support 47 summer interns in 2025! We aim to accept even more of the several thousand who will apply for summer 2026.
Amanda Peet Shares Breast Cancer Diagnosis
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Katie Couric on aging, being a grandmother and the importance of early cancer screenings
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At age 41, a Westmoreland mom of 3 is diagnosed with a cancer that's rising in younger populations
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Department of Health retracts claim sunbeds are as dangerous as smoking
DHSC corrects statements after regulator intervenes as experts say smoking causes far more cancer cases
New AI tool predicts cancer spread with surprising accuracy
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Scientists turn probiotic bacteria into tumor-hunting cancer killers
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Chadwick Boseman's widow shares details of his cancer journey and death: 'A betrayal of faith'
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NCI Director Anthony Letai appeared before the National Cancer Advisory Board Committee March 17 to maneuver through thorny topics while reiterating his message of reassurance: Stability. Stability. Stability. NCI is sturdy and will weather the storms. “The mission hasn’t changed at the National Cancer Institute,” Letai said in his remarks to the committee. “The resources […]
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Sports writer and photographer win Quill awards for work for Guardian Australia
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Men are losing a key chromosome with age and it may be deadly
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Temple Health Appoints Robert A. Winn, MD, as Cancer Center Director for Fox Chase Cancer Center
Temple Health today announced the appointment of Robert A. Winn, MD, as the next Cancer Center Director for Fox Chase Cancer Center, marking a defining moment that will shape the future of one of the nation’s leading National Cancer Institute-designated Comprehensive Cancer Centers.
'In Good Health': Why Is Colorectal Cancer Affecting Generations Differently?
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FDA pulls proposed rule barring teens from indoor tanning
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Colon cancer leading cause of cancer-related death for people under age 50
Thymus may be critical to adult health
Research indicates the often-overlooked organ can be key predictor in longevity, disease risk, and cancer treatment outcomes.
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Thymic health and immunotherapy outcomes in patients with cancer
Nature - A deep-learning approach applied to routine CT scans is used to quantify the health of the thymus in a cohort of patients with cancer, and shows that thymic function is associated with...
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White House chief of staff Susie Wiles has early stage breast cancer, Trump announces
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Smart Plants in a Changing World Science
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Scientists say this simple diet change could transform your gut health
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SGMC Health Welcomes Centers as Director of Pearlman Cancer Center
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Five Global Teams Awarded $125 Million to Take on the Toughest Challenges at the Frontiers of Cancer Science
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A History of HeLa Cells: How the Immortal Cells Advanced Biomedical Science
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Homologous recombination deficiency and hemizygosity drive resistance in breast cancer
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Scientists find the genetic switch that makes pancreatic cancer resist chemotherapy
Scientists have identified a crucial molecular switch that decides whether pancreatic cancer cells resist chemotherapy or respond to it. The key player, a gene called GATA6, keeps tumours in a more structured and treatable form—but it gets shut down by an overactive KRAS-driven pathway. When researchers blocked that pathway, GATA6 levels rebounded and cancer cells became more sensitive to chemo. The discovery could help turn some of the toughest pancreatic tumours into ones doctors can better control.
Actor and Cancer Advocate Patrick Dempsey Partners with Guardant Health to Raise Awareness about Colorectal Cancer Screening and Shield Blood Test, Sharing His Experience Getting Screened
1 in 3 eligible Americans avoid colorectal cancer (CRC) screenings because traditional methods are viewed as unpleasant and inconvenient Guardant's FDA-approved Shield blood test offers an easier, more convenient way to screen with a blood draw from any prescribing healthcare provider for adults 45+ at average risk for CRC Motivated by his mother’s cancer fight, Dempsey is calling on Americans to prioritize getting screened this CRC Awareness Month Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company, today announced its partnership with actor and cancer advocate Patrick Dempsey to increase awareness about colorectal cancer (CRC) screening and the Shield® blood test. Approved by the U.S. Food and Drug Administration (FDA) in 2024 and recommended in national guidelines , Shield offers an easier way to screen for colorectal cancer (CRC) with just a blood draw for eligible individuals 45 and over at average risk for the disease. Patrick Dempsey, actor and cancer
Actor Bruce Campbell announces cancer diagnosis
Star of The Evil Dead franchise Bruce Campbell announced Monday that he is battling a “treatable” but “not curable” form of cancer. Campbell did not reveal the type of cancer he is battling, but sa…
Quarter of healthy years lost to breast cancer are due to lifestyle factors, research finds
Largest study of its kind suggests high red meat consumption has biggest impact, followed by smoking
Which is worse, a soda or a beer?
Experts seek to clarify the health effects of alcohol and sugary drinks.
Experience pop folk magic with Dar Williams at the Englert
Singer-songwriter Dar Williams’ forthcoming studio album, “Hummingbird Highway,” illustrates a period of rebirth and renewal in 2025. Despite a challenging battle with breast cancer and political unrest, Williams demonstrates resilience and gratitude.
Two Cancers Have Links With Talc. An Expert Explains The Science.
Should you stop using it?
How financial and practical stressors can affect emotional health during cancer care
A cancer diagnosis changes almost everything—but it doesn't stop life's other responsibilities. Bills still arrive. Work still needs attention. Family routines keep going. Trying to keep up with it ...
Colon cancer: rectal cancer on the rise in young people
Colon cancer is now the deadliest cancer for people under 50, and researchers are scrambling to understand why rectal cases are driving the trend.
Varsity Blues' Ali Larter Speaks Out on James Van Der Beek’s Death
Dawson’s Creek star James Van Der Beek was remembered at the 2026 Actors Awards March 1, two weeks after his family confirmed he had died from stage 3 colorectal cancer.
Scientists reveal why a popular anti-aging compound may also fuel cancer
Polyamines—natural molecules found in every living cell—have become stars in the longevity world for their ability to boost cellular cleanup and support healthy aging. But there’s a dark twist: high levels of these same molecules are consistently seen in cancer, where tumors grow aggressively.
20-year-old had stomach pain for months, diagnosed with colon cancer
A 20-year-old woman experienced on-and-off stomach pain, then sudden nausea and chills. She was diagnosed with stage 2 colon cancer.
HPV-related throat cancers are rising in men, Louisiana doctors say. Here's what to know.
Incidence rates are rising for HPV-related throat cancers, according to the American Cancer Society, particularly in men over the age of 55. Here's what to know.
New iron nanomaterial wipes out cancer cells without harming healthy tissue
Scientists at Oregon State University have engineered a powerful new nanomaterial that zeroes in on cancer cells and destroys them from the inside out. Designed to exploit cancer’s unique chemistry—its acidity and high hydrogen peroxide levels—the tiny iron-based structure sparks not one but two intense chemical reactions, flooding tumors with cell-damaging oxygen molecules. This dual attack overwhelms cancer cells with oxidative stress while sparing healthy tissue.
New iron nanomaterial wipes out cancer cells without harming healthy tissue
Scientists at Oregon State University have engineered a powerful new nanomaterial that zeroes in on cancer cells and destroys them from the inside out. Designed to exploit cancer’s unique chemistry—its acidity and high hydrogen peroxide levels—the tiny iron-based structure sparks not one but two intense chemical reactions, flooding tumors with cell-damaging oxygen molecules. This dual attack overwhelms cancer cells with oxidative stress while sparing healthy tissue.
Daily habit doesn't help prevent colorectal cancer, scientists warn — and it 'comes with immediate risks'
I'm 56 and I regularly go clubbing with my kids
A mom shares how attending musical theatre club nights with her four daughters helped her family heal through cancer and mental health struggles.
Your morning coffee could one day help fight cancer
Scientists at Texas A&M are turning an everyday pick-me-up into a high-tech medical switch. By combining caffeine with CRISPR gene editing, researchers have created a system that allows cells to be programmed in advance — and then activated simply by consuming a small dose of caffeine from coffee, chocolate, or soda. The approach, known as chemogenetics, lets scientists precisely turn gene-editing activity on and off inside targeted cells, including powerful immune T cells that can fight cancer.
Scientists discover microbe that breaks a fundamental rule of the genetic code
Scientists at UC Berkeley have discovered a microbe that bends one of biology’s most sacred rules. Instead of treating a specific three-letter DNA code as a clear “stop” signal, this methane-producing archaeon sometimes reads it as a green light—adding an unusual amino acid and continuing to build the protein. The result is a kind of genetic coin flip: two different proteins can emerge from the same code, influenced partly by environmental conditions.
Federal panel behind cancer screening recommendations hasn't met in nearly a year
The U.S. Preventive Services Task Force's meetings have stalled as Health Secretary Robert F. Kennedy Jr. has reshaped other federal advisory committees.
Vegan diets linked to colon cancer in large new study: what to know
A new study suggests vegan diets may be lacking some nutrients that help shield people from colon cancer. Fortification could help.
Oregon poised to become first in US to remove cost barriers to cervical cancer detection
The measure would require insurers to fully cover follow-up tests for cervical cancer after an abnormal screening.
Correlation isn't causation: What headlines often get wrong about health science
Headlines can confuse correlation for causation: Tylenol causes autism. Ultra-processed foods cause cancer. Social media causes depression.
4 myths about women's health
Do women really need to focus on cardio? Worry about heart health? Do a yearly mammogram? Meghan Rabbitt, author of the new book The New Rules of Women's Health, sets the record straight.Find the BCRAT calculator here: https://bcrisktool.cancer.gov/Follow us on Instagram: @nprlifekitSign up for our newsletter here.Have an episode idea or feedback you want to share? Email us at lifekit@npr.orgSupport the show and listen to it sponsor-free by signing up for Life Kit+ at plus.npr.org/lifekit
Science for Living: Can using AI risk prediction in breast cancer screening improve early detection?
Researchers at UMass Chan Medical School are studying how an AI-based risk assessment tool could improve early breast cancer detection.
Entertainment This Week with Mike Marra
Airdate: February 25th, 2026 Willbee Transit Mix Previews HBAJ Home & Garden ShowFebruary 25, 2026Chamber Announces Women’s Week Panel Discussion BreakfastFebruary 25, 2026Henry Ford Wellness Wednesday: Cancer Screening with Tumor Board Director Donna Long, RNFebruary 25, 2026Jackson Fire Department Offering Free Smoke AlarmsFebruary 25, 2026Entertainment This Week with Mike MarraFebruary 25, 2026New Downtown Parking Plan…
Science is winning the war on cancer
Our podcast on science and technology. A better understanding of how cancer develops in human cells is leading to new ways to prevent it
This Looming Drug Development Gap Could Impact Patients' Health
In this week’s edition of InnovationRx, we look at cheaper biologic drugs, Novo Nordisk’s $2 billion next-gen obesity drug deal, new ways of fighting cancer, and more.
START Appoints Dr. Frank Smith President of its XenoSTART Preclinical Research Business Unit
/PRNewswire/ -- The START Center for Cancer Research ("START") today announced the appointment of Frank Smith, PhD, MBA, as President of XenoSTART, its...
Mom of 2 Died from Asbestos-Related Cancer After Hugging Her Dad as a Child Exposed Her to the Fibers
Elaine Ellery was exposed to asbestos on her father’s work clothes as a child, which later resulted in her death at 67, a court was told on Feb. 16
HMSA Proposal: Hawaiʻi Health Care Could See Radical Transformation
Changes could touch 760,000 HMSA members and their doctors.