🧬 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

🧬 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…

🫁 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.…

Bi-specifics: not all created equal. 🧬 Tumor-targeted 🛡️ Immune-redirecting 🔥 Immune-enhancing Solid visual from #ASCO25 #TCE #CancerTreatment

Carcinoma of Unknown Primary: Cancer without a past 🧬 Early dissemination 🛡️Immune editing of the primary 🧪CK20+, CDX2+, SATB2+ → treat colon-like 🧭Let biology, not anatomy, guide therapy Not a diagnostic failure — a metastatic strategy. nejm.org/doi/full/10.1056/NE… #ASCO25 #CUP #CancerBiology

Machine & deep learning (#ArtificialIntelligence techniques) will be crucial to interpret large multi-dimensional datasets encompassing pathomic, radiomic, genomic, proteomic data, etc. This review focus on #immunotherapy biomarkers. annalsofoncology.org/article…

If you ever wondered what is: the total mass, number, & distribution of immune cells in the human body, this is a must read. Lymphocytes & neutrophils account each for 40% of all immune cells, while macrophages account for 10%. pnas.org/doi/full/10.1073/pn…