Physician-Scientist https://xitter.twitterapi.xyz/t.co/8RMRruPhfx Discovered p21(WAF1), TRAIL DR5, TIC10/ONC201; 1st ever FDA approval for H3K27M-glioma IU Physician-MBA Class '28
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Books I have edited that may be of interest to those who study cancer. They are all available on Amazon.
Mapping Big Data’s Linkage Challenges for 2026👇
In my Business Analytics Class last night in a lecture by Professor Chris Harle that is part of the IU Kelley School of Business Physician MBA Program, we learned a bit about electronic data sources from Griffin Weber, Kenneth Mandl and Isaac Kohane “Finding the Missing Link for Big Biomedical Data” JAMA, 2014 (Published Online: June 25, 2014: 2014;311;(24):2479-2480.
doi:10.1001/jama.2014.4228). I asked my Claude AI Assistant to prepare a brief summary of what changed between 2014 - 2026.
Here is the output along with 3 slides plus the original image from Weber et al.
The five biggest changes since 2014:
•The structured/unstructured line has blurred. In 2014, notes, images and reports sat on the far side of a wall; large language models and ambient AI scribes now turn free text into codable data at scale. The right-hand column is now "AI-readable," not "out of reach."
•Linkage became plumbing, not probability. Weber's figure relied on probabilistic matching. Today, Cures Act–mandated FHIR APIs, the TEFCA national exchange network, and privacy-preserving tokenization link records across EHRs, claims, labs and registries without exchanging names.
•Genomics moved from SNP arrays to the clinic. Tumor NGS, ctDNA and multi-omics are now routine structured EHR data. In 2014, the genetics row was mostly 23andMe.
•Patients generate continuous data. Wearables, CGMs, ePROs and portal messages have filled the "symptoms" and "lifestyle" rows. In 2014, the figure could only infer those from OTC purchases.
•Codes and real-world data matured. The US switched from ICD-9 to ICD-10 in 2015. SDOH Z-codes, EHR-wide research networks and oncology real-world data platforms now support regulatory-grade evidence.
The privacy concern Weber raised has grown along with the data. Tokenized records can still be re-identified, and 23andMe's 2025 bankruptcy and sale showed that consumer data can change hands. The main question in 2026 is how to govern the linkage that is now possible, not how to make it possible.
My review of this information is that it is accurate and useful and I approve it as teaching, not medical advice or a recommendation for anything.
@KelleyBizMed @BrownUniversity @WIN_Consortium @oncodaily
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Causal Meta-Analysis: Rethinking the Foundations of Evidence-Based Medicine
hdsr.mitpress.mit.edu/pub/um…
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Saturation genome editing of BRCA1 across cell types improves interpretation of variant pathogenicity
nature.com/articles/s41588-0…
An integrated breast cancer transcriptomic atlas defines clinical subtypes and informs cellular origin
Cell Reports Medicine, released November 3, 2026 · Xin Sun … Brian Lehmann (Vanderbilt-Ingram) ·
Classification / cell of origin
More than 7,600 tumors from 22 studies harmonized into one atlas, with several findings that cut against current categories: ER-low tumors behave like ER-negative rather than ER-positive disease; a HER2-positive subset is strongly HER2-signaling-dependent and may respond to HER2 kinase inhibitors; a cryptic neuroendocrine form does poorly after chemo-endocrine therapy and is proposed to be FGFR1-targetable; and a basal-luminal progenitor TNBC subtype looks vulnerable to RTK/MAPK and anti-angiogenic agents. A classifier that runs on standard bulk RNA-seq is released with it. Lehmann's line in the Vanderbilt release: "Some of the most important findings came from tumors hiding in plain sight."Retrospective and transcriptome-only; every therapeutic inference is a hypothesis.
cell.com/cell-reports-medici…
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A Library of Potent TCRs Derived from Healthy Donors Targeting Kras G12d and G12v Neoantigens
Cancer Immunology Research, online November 10, 2026 · Margaret M. Blythe … Kendra C. Foley · KRAS neoantigen targeting
A healthy-donor-derived TCR library against mutant KRAS covering roughly a quarter of pancreatic and about 10% of colorectal patients, with binding and killing comparable to benchmark TCRs. Two useful details: some G12V-reactive TCRs on HLA-C*01:02 also recognize wild-type sequence, with the therapeutic window resting on lower wild-type abundance and still unproven; and G12V is recognized interchangeably on HLA-C*03:03 and C*03:04, which makes it a single, common neoantigen rather than two. A reagent resource, not yet a therapy.
doi.org/10.1158/2326-6066.CI…
Longitudinal Surgical Modeling of Early Glioblastoma Recurrence Reveals Emergence of Margin-Associated Neural Programs
Cancer Research, online November 11, 2026 · Adarsha P. Malla … Graeme F. Woodworth · Recurrence biology / neuron–glioma signaling
Most glioblastoma models never undergo the operation that defines the disease. A miniaturized neurosurgical platform (Maximal Safe Intracranial Surgery) performs resection, multiregional biopsy and repeat sampling in mice across five orthotopic models, reproducing the post-surgical state: extent of resection tracked with survival as it does in patients, and recurrence patterns differed by model. Comparing primaries with their post-surgical recurrences showed enrichment of margin transcriptional states tied to neuron–glioma signaling — a mechanistic handle on the margin population the Sanger atlas above independently flags. A platform paper, so the biology is a first pass.
doi.org/10.1158/0008-5472.CA…
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Latent Squamous Plasticity Licensed by Chromatin-State Remodeling Dictates Therapeutic Susceptibility in Cholangiocarcinoma
Cancer Discovery, online November 11, 2026 · Chen Yang … Cun Wang · Lineage plasticity / immunotherapy resistance
A squamous transition potential index identifies 20–30% of intrahepatic cholangiocarcinomas as harboring squamous plasticity invisible on routine histology, with outcomes resembling overt adenosquamous disease. FOSL1 remodels chromatin to license the program and partners with p63 to raise PTGS2/COX-2; the resulting PGE2 drives neutrophil-dependent polarization of FOXP3-negative Tr1 cells, which is the proposed basis of immunotherapy resistance. A repurposing screen points to celecoxib, now in a phase Ib/II trial (NCT07632235). The index needs prospective validation before it can select patients.
doi.org/10.1158/2159-8290.CD…
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Tumor Cells Hijack Coagulation Signaling to Enable Immune Escape and Metastatic Dissemination
Cancer Research, online November 9, 2026 · Shuang Wang … MuYan Cai · Metastasis / immune evasion
In gastric cancer, tissue factor (F3) links nodal metastasis to immune suppression through a non-coagulant route: the F3 intracellular domain binds eEF1A1, driving STAT3 phosphorylation and CCL20 expression, which recruits CCR6+ regulatory T cells. High F3 tracked with nodal spread, poor checkpoint-blockade response and worse survival. Notably, the approved drug olsalazine disodium disrupted the axis in preclinical models — slowing growth, cutting Treg infiltration and restoring checkpoint sensitivity without altering basal coagulation, which is the part that makes this immediately testable.
doi.org/10.1158/0008-5472.CA…
A stroma-sensing TGF-β blockade reprograms CAF-myeloid niches to induce durable tumor immunity
Cancer Cell, online November 9, 2026 · Dong Woo Kang … Seong-Jin Kim (MedPacto, Seoul; GILO Institute; release via University Hospitals Cleveland) · Tumor microenvironment / boosting immunity
A TGF-β trap (FEBP-sTβRII) is fused to a peptide that binds a tumor-restricted fibronectin isoform, so the drug concentrates and persists in stroma instead of acting systemically. Loosening the fibrotic barrier lets cytotoxic T cells in; their interferon-γ then converts CAFs and neighboring myeloid cells into antigen-presenting allies, which is what makes the effect durable. Tumors cleared in 75% of mice in one aggressive pancreatic model, 7 of 8 were alive at 270 days after treatment stopped, cured mice rejected rechallenge and often rejected bladder and lung tumors as well; the untagged trap altered 693 blood genes versus 25 for the targeted version and did little to tumors. All preclinical, the 75% is one model of three, systemic TGF-β blockade has failed repeatedly in the clinic, and the authors hold patents and MedPacto ties; first-in-human is slated for 2027.
cell.com/cancer-cell/fulltex…
Wafik S. El-Deiry, MD, PhD, FACP retweeted
Somewhere, a brilliant physician-scientist is on module 14 of 22 instead of curing cancer.
We built n1.care to turn your patients’ #scatteredrecords into one clinician-verified timeline.
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The issue of steps and clicks isn’t just in clinical work. In academia, it extends to regulatory oversight from human subjects research, IRB’s, IACUC’s, and other forms of oversight. The frequency and burdens of training modules that are increasingly too detailed, inclusive of irrelevant material, or redundant and even formal attestations by physicians every 3 months verifying that they have not committed crimes to keep practicing medicine is too much. If there is no pushback with regulatory oversight, the tendency is for things to only get worse. Many things are so incredibly inefficient now from the user’s point of view and that point of view is hardly taken into account by system designers or for that matter the government. We can’t lead the world in science and medicine through inefficiency. There is a human cost to solving bureaucratic problems versus pursuit of creative breakthrough science or quality patient care. For those who bridge fields including broadly basic science and multiple fields within medicine, the future needs to address these issues. I believe we need to support the careers of physician-scientists and over time, funding issues aside, I am increasingly concerned about regulatory burdens and inefficiencies. @AAMCtoday @the_asci @ASCO
linkedin.com/posts/wafike_a-…
HuBMAP Data Portal: a resource for multimodal spatial and single-cell data of healthy human tissues
nature.com/articles/s41467-0…
Decoding neutrophil spatial heterogeneity and clinical implications in breast cancer
pubmed.ncbi.nlm.nih.gov/4300…
Blocking serotonin receptors makes eye cancer cells sensitive to drugs
news-medical.net/news/202611…
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Moderna’s CEO eyes Keytruda-eclipsing future for personalised cancer vaccine
Analysts have placed intismeran as central to Moderna’s long-term growth beyond infectious diseases.
pharmaceutical-technology.co…
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Financing Cancer Discovery Research: Models to Accelerate Breakthroughs
milkeninstitute.org/content-…
Arcotatug Tavatecan Offers Manageable Safety in Advanced Gastric Cancer
targetedonc.com/view/arcotat…
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