Chromothripsis explains rapid cancer mutation

Broadcast from KSQD, Santa Cruz on 12-18-2025:

• Dr. Dawn opens by examining how market competition is actually working in the weight loss drug sector. Novo Nordisk's Ozempic and Wegovy compete against Eli Lilly's Monjaro and ZepBound, with prices dropping nearly 50% as companies launch direct-to-consumer websites. The main barriers remain needles and refrigeration, driving development of oral versions. Novo's Wegovy pill awaits FDA approval for early 2026 launch at $150 monthly. Next-generation drugs show remarkable results: Eli's retatrutide causes 24% weight loss in 48 weeks, while Novo's Cagrisema combines semaglutide with amylin to reduce muscle loss. Pfizer paid $10 billion for Metsera's once-monthly drug despite significant side effects.
• A quick fiber tip suggests adding plain psyllium to morning coffee for cardiovascular and microbiome benefits. Start with half a teaspoon and work up to two teaspoons (10 grams) over several weeks to avoid gas. The prebiotic fiber improves glucose tolerance and may reduce cancer risk.
• UC San Diego scientists discovered why cancers mutate so rapidly despite being eukaryotic cells with protected chromosomes. The answer is chromothripsis, a catastrophic event where the enzyme N4BP2 literally explodes chromosomes into fragments. These reassemble incorrectly, generating dozens to hundreds of mutations simultaneously and creating circular DNA fragments carrying cancer-promoting genes. One in four cancers show evidence of this mechanism, with all osteosarcomas and many brain cancers displaying it. This explains why the most aggressive cancers resist treatment.
• Research from 2013 shows any glucocorticoid use significantly increases venous thromboembolism risk, with threefold increases during the first month of use. The risk applies to new and recurrent clots, affecting both oral and inhaled steroids, though IV poses highest risk and topical the lowest. Joint injections fall somewhere between inhaled and oral. Anyone with prior blood clots should avoid steroids except for life-threatening situations like severe asthma attacks requiring ventilation.
• A meta-analysis of 20 randomized controlled trials shows creatine supplementation helps older adults (48-84) maintain muscle mass when combined with weight training two to three times weekly. The supplement provides no benefit without exercise. Recommended dosing starts at 2 grams and works up to 5 grams daily. Vegans benefit most since they consume little meat or fish. Important caveat: creatine throws off standard kidney function tests (creatinine), so users should request cystatin C testing instead for accurate renal health assessment.
• A new JAMA study suggesting risk-based mammogram screening is fatally flawed. First, researchers offered chemopreventative drugs like tamoxifen only to the high-risk group, contaminating the study design. Second, the demographics skewed heavily toward white college-educated women, missing the reality that Black women face twice the risk of aggressive breast cancer with 40% higher mortality. Third, wild-type humans failed to follow instructions—low-risk women continued getting annual mammograms anyway while high-risk women skipped recommended extra screenings. The conclusion of "non-inferior" outcomes is meaningless given poor adherence. Stick with annual mammograms, and consider alternating with MRIs for high-risk women.
• The EAT-Lancet report condemns red meat based purely on observational data showing correlations with heart disease, cancer, and mortality. But people who eat lots of red meat differ dramatically from low consumers: they weigh more, smoke more, exercise less, and eat less fiber. Studies can't control for sleep quality, depression, or screen time. Notably, heavy meat eaters also die more in accidents, suggesting a risk-taking lifestyle phenotype. The inflammatory marker TMAO is higher in meat eaters, but starch is also pro-inflammatory. Eating red meat instead of instant ramen might improve health. A balanced diet with limited amounts beats epidemiology-based blanket statements.
• Dr. Dawn grades Dr. Oz's performance as CMS administrator. Starting at minus one for zero relevant experience, he earns plus two for promoting diet, exercise, and gut health on his show. He studied intensively after nomination, calling all four previous CMS directors repeatedly and surrounding himself with experienced staff (plus one). He finalized Medicare rules favoring prevention over surgery and earned bipartisan praise as "a real scientist, not radical" (plus one). He divested healthcare holdings but kept some blind trust interests (minus 0.5). He's developing a CMS app and partnering with Google on a digital health ecosystem (plus one), but supports ending ACA subsidies that will raise premiums for millions (minus one). He correctly promoted COVID vaccines and contradicted Trump's Tylenol-autism claims (plus one). Final score: 3.5 out of 5 possible points, the only positive score for any Trump health administrator.