CAR T cell therapies for GI cancers: overcoming challenges in clinical trials

Liquid Biopsy as a Prognostic Marker in EGFR-Mutated Oligoprogressive NSCLC A recent study contributed to by Oscar Arrieta and colleagues, published in Lung Cancer (September 2025), investigated how liquid biopsy can help stratify risk in oligoprogressive EGFR-mutated non-small-cell lung cancer (NSCLC). The retrospective study included 84 patients treated with EGFR-TKIs and local therapy at the time of oligoprogression. Results showed that liquid biopsy positivity indicating the presence of circulating tumor DNA (ctDNA) was strongly associated with worse progression-free and overall survival in patients with extracranial oligoprogressive disease (OPD). Interestingly, this correlation was not observed in central nervous system (CNS) oligoprogression. Multivariate analysis confirmed that liquid biopsy positivity was the only independent prognostic factor for outcomes following oligoprogression. These findings highlight the prognostic value of liquid biopsy in identifying patients who could benefit from continued TKI therapy combined with local treatments, offering new perspectives for personalized NSCLC management. We recognize Oscar Arrieta, Alberto Guijosa, Eduardo Rios-Garcia, and collaborators for advancing precision oncology in EGFR-mutated NSCLC. 📖 Read the full article: https://lnkd.in/dmKwEAhV #OncologyFrontier #LungCancer #NSCLC #EGFR #LiquidBiopsy #PrecisionOncology #OscarArrieta #LungCancerJournal #CancerResearch

Assessing pathological response to neoadjuvant therapy in renal cell carcinoma: a systematic review and guidelines for sampling and reporting standards from the International Neoadjuvant Kidney Cancer Consortium https://lnkd.in/dWGjYPdQ This study systematically reviewed 119 publications on neoadjuvant therapy in renal cell carcinoma (RCC) to evaluate how pathological response is currently assessed and reported. The analysis revealed that only 4% of studies detailed their response assessment methods, and just 7% employed quantitative measures, highlighting a lack of standardization. To address this, an international expert workshop at the Netherlands Cancer Institute in 2024 developed consensus recommendations for tissue preparation and response reporting. The proposed guidelines advocate for standardized specimen sampling, quantification of residual viable tumor in 10% intervals with measurement of greatest linear extent, and inclusion of clinical treatment details. These standardized methods aim to enable consistent evaluation of pathological response in RCC, facilitating research into its correlation with survival outcomes and paving the way toward uniform reporting in future clinical studies. #KidneyCancer James Blackmur  Femke Burgers  Michelle Hirsch Payal Kapur  Rohit Mehra  Priya Rao  Sabina Signoretti  Grant Stewart james jones

These standardized methods aim to enable consistent evaluation of pathological response in RCC, facilitating research into its correlation with survival outcomes and paving the way toward uniform reporting in future clinical studies. #KidneyCancer

💡 This week’s Sunday Papers feature a digest of a small number of recent interesting papers in the field of translatomics. - Diabetes is causally associated with increased breast cancer mortality by inducing FIBCD1 to activate MCM5-mediated cell cycle arrest via modulating H3K27ac. - NSUN2–tRNAⱽᵃˡ⁻ᶜᴬᶜ-axis-regulated codon-biased translation drives triple-negative breast cancer glycolysis and progression. - Downregulation of tRNA methyltransferase FTSJ1 by PM2. 5 promotes glycolysis and malignancy of NSCLC via facilitating PGK1 expression and translation. 🔗 https://lnkd.in/eEBJgtTu #HarnessingTranslatomics #EnablingBioinnovations #RibosomeProfiling #Science #MolecularBiology

🔥 Hot Off the Press | Low-Dose #Aspirin & #PI3K -Altered #Colorectal Cancer Aspirin is known to reduce colorectal adenoma & cancer risk. Recent studies suggest it may also improve disease-free survival, especially in patients with tumors carrying #PIK3CA mutations. 🧪 The Study: A double-blind, randomized trial tested 160 mg daily aspirin vs placebo for 3 years in patients with localized colorectal cancer harboring PI3K pathway alterations. ● Group A: PIK3CA hotspot mutations ● Group B: Other impactful PI3K/PIK3R1/PTEN variants 📊 Results: ● 3-year recurrence:Group A: 7.7% (aspirin) vs 14.1% (placebo)；Group B: 7.7% (aspirin) vs 16.8% (placebo) ● Disease-free survival improved with aspirin in both groups. ● Severe adverse events: 16.8% (aspirin) vs 11.6% (placebo) ✅ Conclusion: Low-dose aspirin significantly lowers colorectal cancer recurrence in patients with PIK3CA hotspot mutations and shows benefit in other PI3K-altered tumors. 🔗 MedChemExpress provides Aspirin for research use only. https://lnkd.in/gpeDcXC3 #ColorectalCancer #PI3K #Aspirin #PrecisionMedicine #ClinicalTrials #Oncology #ALASCCA

Antibody-drug conjugates in metastatic urothelial cancer: Highway to heaven https://lnkd.in/dBDf2ns5 Metastatic urothelial carcinoma (mUC) has long been associated with poor outcomes and limited therapeutic options, but recent advances in tumor biology have driven the emergence of innovative treatments such as immune checkpoint inhibitors and antibody-drug conjugates (ADCs). ADCs like enfortumab vedotin, sacituzumab govitecan, and trastuzumab deruxtecan have transformed the therapeutic landscape by enabling targeted cytotoxic delivery to tumor cells. This review explores the evolving role of ADCs in mUC, focusing on their mechanisms of action, clinical efficacy, patient selection, molecular insights, and the potential for personalized therapeutic strategies in this rapidly advancing field. #BladderCancer Alberto D’angelo  Martina Catalano

Very Concerned about the contents of my correspondence that has been published in The Lancet Oncology -Synthetic progestin use and young-onset breast cancer https://lnkd.in/gwEdgFNS Katie O’Brien and colleagues’ pooled cohort analysis demonstrates that oestrogen plus synthetic progestin therapy is disproportionately associated with ER-negative and triple-negative breast cancers (TNBC) in younger women (16–54 years). TNBC is among the most aggressive and therapeutically challenging breast cancer subtypes https://lnkd.in/ge3mcxud Why might this be happening? Research — including our own — suggests that the androgen receptor (AR) functions as a tumor suppressor in breast tissue, working in cooperation with GATA3 to maintain luminal differentiation. Synthetic progestins, however, can disrupt AR signaling, removing this critical brake and potentially shifting breast cells toward a basal-like, TNBC phenotype. This raises urgent questions: Girls are menstruating earlier, and synthetic progestins are increasingly prescribed to regulate bleeding during active breast development, are we inadvertently creating conditions that expand stem cell populations predisposed to TNBC? Could this risk be particularly significant in ethnic subgroups — such as African American women — already facing a disproportionate TNBC burden? By contrast, the WHI HRT study involved women ~20 years older, with more quiescent breast tissue, where hormone therapy was linked mainly to receptor-positive cancers. Timing matters. This context underscores the importance of HAV-088 — a bioidentical testosterone plus aromatase inhibitor implant — currently under investigation in the DCIS ReCast Trial. By preserving AR signaling, HAV-088 may offer a pathway not only to reduce mammographic breast density and background parenchymal enhancement but also to provide tumor-suppressive benefit at the earliest stages of disease. The hypothesis is compelling and concerning: synthetic progestins may fuel TNBC risk, while therapies that support AR function could open a safer, more effective preventive strategy. We urgently need preclinical and epidemiological studies to prove — or disprove — this. #BreastCancer #androgenreceptor #DCIS

Thank you prof Birrell for sharing this post. A new Lancet Oncology study has reignited debate about hormone therapy and breast cancer risk in younger women. Pooled data from nearly half a million participants show that estrogen + synthetic progestin therapy may modestly increase the risk of young-onset breast cancer, particularly with longer use and in women with intact uterus/ovaries, while estrogen-only therapy appeared neutral or even protective. Importantly, the excess risk was most evident for more aggressive subtypes such as ER-negative and triple-negative cancers. These findings don’t warrant alarm, but they do highlight the need for careful, individualized prescribing, lowest-dose/shortest-duration strategies, and open discussion with patients about benefits, risks, and alternatives

Immune Checkpoint Inhibitors in Solid Organ Transplant Recipients: Clinical Insights Dr. Muntaser Zyoud and colleagues presented their work at the 2025 ASCO Annual Meeting, delivering a systematic review and meta-analysis exploring the safety and efficacy of immune checkpoint inhibitors (ICIs) in solid organ transplant recipients. This analysis, covering over 330 transplant recipients, addresses the key concern of transplant rejection, with the highest rates observed in kidney recipients and the lowest in liver recipients. Importantly, the findings highlight that rejection risk can be reduced with pre-transplant ICI administration, longer washout periods, and anti-CTLA4 therapy, crucial insights for clinicians striving to balance cancer control with graft survival. This research provides a foundation for better treatment strategies and emphasizes the importance of multidisciplinary collaboration in managing cancer in transplant patients. 🔗 Read more about Dr. Muntaser Al Zyoud’s presentation:https://lnkd.in/dp7zmZsp #ASCO25 #OncologyFrontier #CancerResearch #Immunotherapy #TransplantMedicine #ICIs #CancerCare #ClinicalOncology #MuntaserAlZyoud

📄 Combining Epigenetic Modulation: The Next Step for HCC Immunotherapy? In a recent Gut commentary, Dr. Chi Ma (NIH) and Professor Bertram Bengsch (University of Freiburg) explore an exciting approach to overcoming resistance to immune checkpoint blockade (ICB) in hepatocellular carcinoma (HCC). They highlight preclinical findings from Tu et al., showing that HDAC inhibitors combined with ICB can enhance CD8⁺ T-cell responses and trigger tumour cell pyroptosis in ICB-resistant HCC. This strategy could potentially expand the proportion of patients who benefit from immunotherapy—particularly those with immune-excluded or “cold” tumour microenvironments. As cancers are driven by epigenetic reprogramming, targeting chromatin accessibility may open a new therapeutic window to boost antitumour immunity and improve survival outcomes in advanced HCC. https://lnkd.in/eDr5ecwH #HCC #LiverCancer #Epigenetics #HDAC #Immunotherapy #Oncology #OncologyFrontier #CancerResearch #PrecisionMedicine #CheckpointInhibitors