Great graphics and global overview on cancer prevalence and therapeutic improvements in this article. Overall cancer survival rates have moved from 50% end of the 70s to 67% in 2013. ourworldindata.org/cancer

🧬 Early-onset colorectal cancer: a distinct tumor ecosystem? • 🌐 Stromal enrichment: Younger MSS tumors exhibit ↑ stromal/epithelial ratio, validated in 712 tumors. • 🔀 EMT signaling: ↑ inferred FN1, GDF, ACTIVIN & SPP1 interactions suggest enhanced tumor–stroma crosstalk. • 🧬 Transcriptional rewiring: ↑ lncRNA expression, including poorly characterized transcripts, in younger MSS tumors. • 🔬 Genomic landscape: CNA patterns largely conserved across ages, with a trend toward greater intratumoral heterogeneity (P=0.056). • 🎯 Therapeutic opportunities: Stromal remodeling & EMT-associated signaling emerge as potential vulnerabilities. 📄 doi.org/10.1038/s41591-026-0…

🧬 Cancer Progress 2026: remarkable gains & a rapidly evolving therapeutic frontier fueled by science • 📉 Mortality: US cancer death rate ↓ 35% since 1991 → >4.8M deaths averted • 💊 Innovation: 11 new anticancer therapies FDA-approved in the past 12 months—10 molecularly targeted, including the first PROTAC in breast cancer • 🛡️ Immunotherapy: 15 ICBs now span 23 cancer types • 📈 Survival: 5-year survival across cancers reached 71% versus 49% in the mid-1970s cancerprogressreport.aacr.or… #AACR

AI in Pharma R&D: time to move from better models → better medicines • 🎯 Optimize what matters: improving Phase II success has far greater potential impact than simply accelerating hit discovery • 💊 Ligand ≠ drug: AI can generate binders rapidly—but efficacy requires the right biology, exposure, safety & patient • 🧬 Better data ≠ more data: biological data are highly contextual; what matters is predictive validity for human outcomes • 📊 Benchmark ≠ impact: model accuracy matters only if it improves a real R&D decision—advance, redesign or stop • 🔄 Next frontier: start with the clinical question → generate fit-for-purpose human biology → integrate clinical feedback → continuously improve the model 👉 Perhaps the end of the beginning: less “technology push,” more “science pull.” #AI #DrugDiscovery #DrugDevelopment #PrecisionMedicine nature.com/articles/s41573-0…

🦠 Programmable bacteria as cancer immunotherapy? A fascinating new study in STM 👏 Congratulations to Mathieu Rouanne, Nicholas Arpaia, & colleagues. 🔬 Engineered E. coli Nissle delivering CXCL13 directly into the bladder: • Recruited & organized B- and T-cell immunity • Induced tumor-specific antibodies • Synergized with PD-1 blockade • Produced durable tumor control and long-term survival in preclinical bladder cancer models A compelling example of how synthetic biology could reshape the tumor immune microenvironment and expand the cancer immunotherapy toolbox. 📄 science.org/doi/10.1126/scit…

🧬 ADC innovation requires payload diversification—not just target diversification. • 🔄 The ADC pipeline is increasingly dominated by TOP1 inhibitor payloads, raising concerns about resistance mechanisms and overlapping toxicities. • 💡 Trastuzumab deruxtecan illustrates that historically unsuccessful cytotoxics can become effective payloads when redesigned for antibody-mediated delivery. • 🎯 Future payload selection should prioritize pharmacologic behavior—proliferation-restricted activity, favorable pharmacokinetics, sustained intracellular target engagement, and controlled bystander effects—rather than maximal in vitro potency. • 🔬 Legacy cytotoxics (e.g., antifolates, nucleoside analogs), degraders, immune-stimulants represent an underexplored source of mechanistically distinct ADC payloads. • 🚀 Broadening payload diversity may expand therapeutic opportunities, delay class-wide resistance, and define the next generation of precision ADCs. doi.org/10.1016/j.trecan.202…

🧬 We've been developing ADCs as targeted drugs. Biology says otherwise. • ❌ Target expression alone poorly predicts benefit • 🔀 ADC efficacy emerges from the interaction between tumor cells, TME, payload, linker, and immune biology • 🧠 Precision ADCs require multidimensional biomarkers—not better IHC • 🧪 Longitudinal biopsies, ctDNA and spatial profiling should become important parts in ADC trials • 🎯 The next generation of ADCs will be defined as much by patient selection as by molecular engineering doi.org/10.1016/j.ccell.2026…

Join the ASCO community of practice on AI in room S103 : great ongoing presentations & discussions #ASCO26

The Topo1 ADC tsunami in ADCs #ASCO26

🧬 Liquid biopsy can now profile the tumor microenvironment (TME) • 🧪 Deep-learning analysis of cfDNA methylation profiles inferred spatial TME ecosystems directly from plasma • 🌐 Plasma-derived “liquid ecotypes” captured distinct immune/stromal ecosystems linked to geography within tumors (margin vs core) • 🎯 Liquid TME profiling predicted ICB response: immune-active SE7/SE8 → benefit; stromal/hypoxic SE4 → resistance • 📊 In melanoma, liquid ecotypes showed stronger survival associations than PD-L1 or TMB in several analyses • 🔄 This enables a new paradigm: serial, non-invasive monitoring of the evolving TME ecosystem during therapy nature.com/articles/s41586-0… #LiquidBiopsy #PrecisionOncology

Lung cancer 2030: from treating disease → intercepting evolution • 🧬 Evolution-guided care: integrate genomics + epigenome + proteome to map tumor trajectories • 🧪 MRD- based trials: ctDNA-driven escalation/de-escalation → treat microscopic disease, not relapse • 🔀 Target plasticity: drug-tolerant persisters & lineage switching as primary therapeutic targets • 🎯 New modalities: ADCs, TCEs, degraders to expand beyond classic oncogene • 🌍 Shift upstream: prevention (IL-1β axis), and risk-adapted screening 👉 Future = anticipate, intercept, and adapt aacrjournals.org/cancerdisco…

🧬 Beyond PD-L1: thymic health emerges as a host determinant of ICB response • 🧠 Host biology matters:thymic health (CT-derived proxy of T cell maturation) predicts outcomes across 3,476 immunotherapy-treated patients • 📉 Clinical impact: high thymic health → ↓progression & ↓mortality (HR ~0.5–0.65) in NSCLC, independent of PD-L1/TMB • 🔬 Mechanistic link: higher thymic health correlates ↑TCR diversity, & ↑circulating T cells • 🌍 Tumor-agnostic signal: predictive across lung, melanoma, breast, renal cancers → complements tumor-centric biomarkers (PD-L1/TMB) nature.com/articles/s41586-0…

🧬 Turning intracellular kinases into druggable surface targets • 🔀 Trafficking switch: Src flips to the surface via autophagolysosomal exocytosis • ⚡ Active outside: eSrc phosphorylates extracellular proteins (e.g., ADAM17) → tumor growth • 🎯 Tumor-selective: present on cancer cells, absent on normal cells • 🧬 Class effect: other lipid-anchored proteins (Lyn, Hck) also exposed • 🧪 Therapeutic angle: enables antibody targeting (TCE, ADC, radioligand) of a “non-druggable” kinase science.org/doi/10.1126/scie…

At #TTLC26, @DRCamidge shared powerful insights shaped by both clinical expertise and personal experience living with #lungcancer. His presentation reminds us why continued innovation in #lungcancer research is essential to improving patient outcomes every day. bit.ly/46YrbUc

🫁 Lung cancer in never smokers: actionable implications for practice • Driver-rich biology: 78–92% actionable (EGFR/ALK); low TMB → limited ICI benefit → perform broad NGS upfront. • Etiology: germline risk (EGFR T790M, APOBEC3A/B), CHIP-driven inflammation, radon, second-hand smoke (~20–25% ↑ risk), PM2.5. (air pollution) • Screening: LDCT benefit proven in smokers; in never-smokers, consider only high-risk subgroups (e.g., family history). • Adjuvant precision: EGFR TKIs improve outcomes post-resection—test early-stage disease. • Prevention horizon: IL-1β targeting and neoantigen vaccines under investigation. sciencedirect.com/science/ar…

🧬 Hallmarks of cancer—what’s new beyond the original 6 • Evading immune destruction is now a core acquired capability, reflecting multi-layered TME immunosuppression and T-cell exhaustion biology. • Deregulating cellular metabolism was added as a hallmark capability (beyond “Warburg”) to capture diverse metabolic rewiring that supports growth and survival. • Unlocking phenotypic plasticity is the newest hallmark (introduced 2022): epigenetic flexibility enabling state switching, heterogeneity, and adaptive resistance. • These “new” hallmarks sit within an expanded framework that also emphasizes hallmark-enabling characteristics, hallmark-conveying TME cells, and systemic interactions. • Original 6 (reminder): sustaining proliferative signaling; inactivating growth suppressors; resisting programmed cell death; establishing replicative immortality; inducing/accessing vasculature; activating invasion & metastasis. doi.org/10.1016/j.cell.2025.…

🧬🛡️ HER2-low tumors escape HER2 ADCs by losing the target • True HER2 loss is uncommon in HER2-amplified disease but frequent in HER2-low, where HER2 isn’t oncogenic • On HER2 ADC therapy, ~50% of tumors reduce HER2; among reducers, ~half become IHC 0 • Reduced HER2 → impaired ADC internalization, not payload resistance • ERBB2 ECD variants disrupt antibody binding and phenocopy antigen loss • Suggested strategy: multi-target payload delivery to bypass target dependence and improve durability aacrjournals.org/cancerdisco…

📊🧬 Cancer in 2026 — key facts for oncologists • Burden: ~2.11M new cancer cases and ~626K deaths projected in the US (2026). • Mortality: Cancer death rates ↓34% since the early 1990s, averting ~4.8M deaths. • Survival: Overall 5-yr relative survival reached 70%(2015–2021), up from 49% in the mid-1970s. • Advanced disease: 5-yr survival for distant-stage cancers improved 17% → 35%, with major gains in lung, melanoma, & rectal cancer. • Unfinished work: Lung cancer remains the leading cause of cancer death acsjournals.onlinelibrary.wi…

Targeted protein degradation in AML is defined by target biology, degrader design, & transcriptional control. Event-driven pharmacology: catalytic MLLT1/3 degradation vs occupancy-based inhibition → sustained pathway suppression. 🖋️Target selection matters: non-enzymatic, scaffold proteins (MLLT1/3) inaccessible to classic inhibitors 🖋️Transcriptional reprogramming: disruption of leukemogenic gene networks → anti-leukemic activity 🖋️Resistance biology: degradation enables single-agent activity & rational combinations to extend remission durability 🖋️Platform relevance: expands small-molecule degradation into hematologic malignancies.

🧬 2025 FDA approvals: oncology still leads—but with a shifting mechanistic profile • Oncology dominates approvals: 16/46 (35%) new FDA drugs in 2025 were cancer therapies—well above any other therapeutic area, reinforcing oncology as the primary engine of regulatory innovation. • MoA trend in oncology: approvals cluster around precision modalities—ADCs (TROP2, c-MET), bispecific T-cell engagers (BCMA×CD3), immune checkpoints (PD-1), & highly selective kinase inhibitors. • Contrast with non-oncology TAs: cardiology, inflammatory & metabolic drugs largely target physiologic pathway modulation (BTK, DPP1, PCSK9, Naᵥ1.8), with fewer cytotoxic or immune-redirecting mechanisms. • Biology-driven cancer approvals: multiple first-in-class or mutation-defined indications (H3 K27M glioma, KRAS-mut ovarian cancer, HER2-mut NSCLC) highlight continued regulatory reliance on molecular stratification. nature.com/articles/d41573-0…

Radio Ligand Therapies: how precision radiation is reshaping oncology 🌊 Tumor-targeting ligands deliver radioactive payloads systemically, irradiating cancer while trying to spare most normal tissue. 🔀 Radionuclide choice matters: β emitters enable crossfire in bulky/heterogeneous disease, α emitters do better in micrometastases. 🛡️ Efficacy depends on target stability, not oncogenic addiction (PSMA, SSTR2, FAP > RTKs) 🧬 Carrier design (small molecules vs antibodies, multimerization, pre-targeting) governs penetration, retention & toxicity. 🧪 Personal dosimetry + early-line use + rational combinations (ADT, PARPi, ICB) may expand the therapeutic window. nature.com/articles/s41571-0…