What if doctors could test cancer treatments on your tumor, without putting a single one of those treatments into your body? CBS News’ Riley Callanan reports.

Small cell carcinoma of the bladder: why ADC targets from conventional UC do not simply carry over, and what may work instead 🧵 New in @Histo_Journal: 88 SmCCB from Milan and Erlangen, 79 fully profiled by IHC for ASCL1, NEUROD1, POU2F3, YAP1, HNF4α, NE and tuft cell markers, plus 7 therapeutic targets and NECTIN4 FISH. 🔬 Two phenotypes 🟢 High-NE (57/79): ASCL1-driven, NEUROD1-driven or mixed, diffuse synaptophysin, chromogranin and CD56 🟠 Low-NE (22/79): POU2F3-driven, YAP1-driven or TF-negative, weak or absent NE markers, significantly associated with admixed urothelial, glandular or squamous histology 🎯 ADC and BiTE targets, one by one Nectin-4 (membranous) • Completely negative in 75% (60/80) • Median H-score 0, mean 11.6, max 220 • Higher in Low-NE than High-NE (median 1.5 vs 0, P<0.001), consistent with retained urothelial differentiation NECTIN4 amplification (FISH) • 16/73 (21.9%), a frequency comparable to conventional UC • No difference between High-NE and Low-NE (P=0.835) • No association with membranous protein (P=0.099) TROP2 • Completely negative across the cohort HER2, FOLR1, Claudin 18.2 • Rare and weak expression only DLL3 • Positive in 35/43 evaluable High-NE cases (81%) • Nearly absent in Low-NE (P<0.001) • Relevant for DLL3-directed BiTEs such as tarlatamab and for DLL3 ADCs in development SLFN11 • Median H-score 125, significantly higher in High-NE (P=0.006) • Supports testing DNA-damaging strategies in this group 💡 Key takeaways 1️⃣ High-NE SmCCB is largely Nectin-4 protein negative, yet carries NECTIN4 amplifications at rates similar to conventional UC. The amplification is present, the protein is not. 2️⃣ Our hypothesis: this points to NE transdifferentiation from a urothelial precursor that already harboured the amplification. The gene status is retained, while the urothelial protein program, including Nectin-4, is switched off during lineage change. The equal amplification rate in both phenotypes fits this model. It needs confirmation in paired and clonal analyses. 3️⃣ Practical consequence: NECTIN4 FISH alone should not be read as a surrogate for target presence in SmCCB. Gene status and membranous protein both need to be assessed. 4️⃣ Enfortumab vedotin benefit cannot be assumed in High-NE SmCCB. Low-NE tumours with residual urothelial features remain the more plausible candidates for UC-type ADCs. 5️⃣ High-NE SmCCB behaves biologically like SCLC: DLL3-high, SLFN11-high. This makes it a rational population for SCLC-directed strategies. 6️⃣ A tuft cell-like subset exists: POU2F3-driven tumours co-express POU2AF2 (11/16) and ChAT (13/16), with preclinical mSWI/SNF vulnerabilities. 7️⃣ A simple workflow (NE markers ± TF panel) can stratify SmCCB in routine diagnostics today. ⚠️ Limits: retrospective, TMA-based, no treatment or outcome annotation. Treatment-annotated and paired pre/post-therapy cohorts are the next step. Big shout out to Nazario Tenace from San Raffaele he drove this work as fellow. Bright future for this talented pathologist. Shout out also at great collaborators from Sann Raffaele @AndreaNecchi @Albert0Briganti @F_Montorsi and @mauriziocollechia @maurilioponzoni @claudiodoglioni and @UroMoschini Great collaboration between San Raffaele Milan and UK Erlangen, led by Nazario Tenace, with @andreanecchi 🔗 doi.org/10.1111/his.70284

#Comment🚨 Swanton&Co @CharlesSwanton highlight the histories of EGFR, HER2, CDK4/6 and RAS, and discusses how sustained investment in discovery science continues to generate clinical benefit through new drugs, indications and treatment combinations. 📖⬇️ dlvr.it/TVPRKl

Every September we mark Prostate Cancer Awareness Month. This year it’s more personal for me. More than 330,000 American men this year will hear the words we did last spring when I was diagnosed with prostate cancer. By the time we found it, it had already spread to my bones. When prostate cancer is caught early, the five-year survival is close to 100%. So have the conversation with your doctor. Don’t put it off. If you're at average risk, that conversation should start around 50, and the guidelines now say screening every 2 to 4 years. If you're a Black man, start it at 45 or earlier. You are nearly 70% more likely to get this disease and 2 to 4 times more likely to die from it. Which is an outrage in the richest country in the world. If your father or your brother had prostate cancer, start the conversation at 45, and even earlier if more than one of them did. I am deeply grateful to the doctors, nurses and other medical professionals who helped to control my cancer and who continue to take such good care of me. Their skill, dedication, and compassion mean so much. The radiation treatment from last fall worked as intended, and I continue to do the things I care about, like finishing my memoir. Thank you to everyone who has reached out and continues to keep me and my family in your prayers. We appreciate every single one of you. It’s my hope and prayer that by sharing our experience and being part of this important conversation, we can help save lives. Talk to your doctors. Ask the hard questions. Do it for yourself, and do it for the people who love you. And no matter what, keep the faith. God bless you.

Personalized mRNA-based neoantigen vaccines + pembo are being tested in a number of randomised adjuvant cancer trials (included bladder and renal). The 1st positive trial (RIII in melanoma) was announced today. PCVs are logistically complex with limited monotherapy activity in advanced disease, but early IO combinations in MRD may overcome tumor microenvironment resistance. Patient selection or even vaccine generation could occur with ctDNA. @OncoAlert merck.com/news/merck-and-mod…

Our next @WCMEnglanderIPM #PrecisionMedicine Research Conference, "Bio-Digital #Avatars for Personalized Sequencing of #BladderCancer Therapies," will be presented by our Chief Research Officer Dr. Bishoy Faltas (@FaltasLab) on Sept. 10th!