Journal Biology of the Cell’s Post

Anti- CEACAM6 antibody+ BET protein degrader conjugate inhibits tumour growth in pancreatic cancer models. https://lnkd.in/g43BaqPm

Eisai Co., Ltd.'s DAC Research 1. Delivering EBET using the CEACAM6 antibody degrades BRD (bromodomain proteins) in CEACAM6-positive pancreatic cancer cells. 2. They regulate pancreatic cancer stromal signaling through a bystander effect on CEACAM6-negative CAFs (cancer-associated fibroblasts). STAT3, a key signaling molecule in CAFs, is functionally linked to BRD2/4, and EBET payloads diffused from pancreatic cancer cells inhibit STAT3 signaling in CAFs. 3. The #84.7 antibody has a lower binding affinity to normal cells like MPCs (myeloid progenitor cells) than existing CEACAM6 antibodies, reducing side effects on normal cells.

The study below investigated a bacterial supplement called Clostridium butyricum MIYAIRI 588 (CBM588) in patients with metastatic kidney cancer. Patients who received CBM588 along with the drugs cabozantinib and nivolumab showed signs of improved clinical outcomes. CBM588 produces butyric acid, essential for gut health and an established immunomodulator. Although the study's primary objective was not met, the objective response rate was significantly higher in participants treated with CBM588. Researchers are planning a phase II/III trial to evaluate the use of CBM588 in patients with advanced cancer. #clinicaltrials https://lnkd.in/dNfW4btn

📢 New article alert: The Role of microRNAs in Hepatocellular Cancer: A Narrative Review Focused on Tumor Microenvironment and Drug Resistance https://lnkd.in/giDeEJWR #WorldLiverDay #livercancer #CancerResearch #openaccess #ecm #oncology

GenFleet Therapeutics announced encouraging results from the Phase II #KROCUS study at the #ASCO24 meeting, showcasing the efficacy of combining #fulzerasib with #cetuximab in treating non-small cell #lungcancer (#NSCLC). The study highlighted an 81.8% objective response rate and a strong safety profile, marking a significant advancement in first-line treatment options for #lung #cancer patients with the #KRASG12C mutation. The data, presented by Dr. Vanesa Gregorc, highlighted that this combination therapy demonstrated promising efficacy and a good safety profile. https://lnkd.in/dpcG_jVp

Ribociclib (Kisqali; Novartis) in combination with an aromatase inhibitor (AI) received FDA approval for the adjuvant treatment of patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) stage 2 and 3 early breast cancer (EBC) at high risk of recurrence. Learn more: https://bit.ly/3MSX2eo

Deleterious association between proton pump inhibitor and protein kinase inhibitor exposure and survival for patients with lung cancer: A nationwide cohort study https://lnkd.in/dvt3Hde7

Another interesting new compound in advanced prostate cancer: ODM-209. #ASCO24 abstract 5060: Prelim results from dose escalation phase 1 study. This is a novel CYP11A1 inhibitor, which blocks production of steroid hormones. 34 patients with metastatic castrate resistant prostate cancer (mCRPC) enrolled.  All had at least one prior round of taxane chemo and at least one prior ARSI (abiraterone, enzalutamide, etc) -  18 (53%) had prior both abi and enza -  18 (53%) had both docetaxel and cabazitaxel chemotherapy -  19 (56%) had AR-LBD mutations This is a patient population in which additional targeting of hormonal axis doesn’t work with routine standard of care and with a very poor prognosis. Results: -   10 (29%) patients had PSA response of 50% or greater; 9 with AR-LBD mutation and 1 without. -   3/11 (27%) with measurable soft tissue disease had tumor shrinkage on scans -   Median duration of treatment in those with AR-LBD mutations was 4.8 months Another “wow” here.  This drug looks active in refractory mCRPC patients with AR-LBD mutations.   Keep an eye on it.

his novel CYP11A1 inhibitor is a significant development in the treatment landscape of metastatic castrate-resistant prostate cancer (mCRPC), especially for patients with AR-LBD mutations. AR-LBD mutations refer to alterations in the ligand-binding domain of the androgen receptor, which allow the receptor to be activated by alternative steroid hormones, leading to resistance against conventional AR-targeting therapies. Key findings from the recent real-world assessment underscore the impact of these mutations: In a large database study, 21% of mCRPC patients treated with AR pathway inhibitors (ARPi) had AR-LBD mutations, with the prevalence increasing after subsequent lines of ARPi therapy. The study revealed that men with AR-LBD mutations were more likely to harbor co-alterations in genes like APC, CTNNB1, PTEN, BRCA2, and ARID1A, which are relevant to tumor progression. Patients with AR-LBD mutations exhibited worse overall survival from first-line mCRPC therapy compared to those without these mutations (50.1 vs. 60.7 months). These insights highlight the clinical significance of AR-LBD mutations and the potential of the CYP11A1 inhibitor to target this resistant and challenging patient population. By addressing AR-LBD mutations, this inhibitor could provide a new therapeutic avenue, enhancing precision medicine strategies and improving outcomes for mCRPC patients. #ProstateCancer #Oncology #CYP11A1Inhibitor #mCRPC #CancerResearch #PrecisionMedicine #ARLBDMutations #OncologyBreakthroughs

Neoadjuvant nivolumab or nivolumab plus LAG-3 inhibitor relatlimab in resectable esophageal/gastroesophageal junction cancer: a phase Ib trial and ctDNA analyses https://lnkd.in/gpfYYvx4