wang hao’s Post

They write: Antibody-based targeted therapy in cancer faces a challenge due to uneven antibody distribution in solid tumors, hindering effective drug delivery. We addressed this by developing peptide mimetics with nanomolar-range affinity for Receptor Tyrosine Kinase-Like Orphan Receptor 1 (ROR1) using computational methods. These peptides showed both specific targeting and deep penetration in vitro and in vivo. Additionally, we created peptide-drug conjugates (PDCs) by linking targeting peptides to toxin drugs via various linkers and enhancing their in vivo half-life with fatty side chains for albumin binding. The antitumor candidate II-3 displayed exceptional affinity (KD = 1.72 × 10–9 M), internalization efficiency, anticancer potency (IC50 = 0.015 ± 0.002 μM), and pharmacokinetics (t1/2 = 2.6 h), showcasing a rational approach for designing PDCs with favorable tissue distribution and strong tumor penetration.

In a study funded by our division, Meisam Bagheri, Ph.D., Todd Miller, PhD, Diwakar Pattabiraman, et al. found that eribulin (an FDA-approved chemotherapeutic drug) induces chromatin remodeling to reverse epithelial to mesenchymal transition and sensitizes cancer cells to other chemotherapies in preclinical models of triple-negative #BreastCancer. https://lnkd.in/erd5cpTu

📢Data release alert! This weekend at the 2024 European Hematology Association (EHA) Conference, Dr. Lisa Ivanschitz, our Associate Principal Scientist, unveiled the latest preclinical data on Debio 1562M - our potential first-in-class CD37 targeted antibody drug conjugate in development for Acute Myeloid Leukemia (AML) and Myelodysplastic syndrome (MDS).   This next generation ADC leverages our MultiLink™ proprietary cleavable linker technology, allowing both high DAR and high stability to efficiently deliver cytotoxic payloads directly to cancer cells.🎯   Curious about this breakthrough? Dive deeper into the science behind it! 👇 #Hematology #Innovation #ADCs #TargetedTherapy #Oncologoy

New article in Forbes online covering a recent review of the evidence for anticancer activity of cannabinoids: https://bit.ly/47XYSEG. "The review also illustrates the need for continued research into cannabinoids and cancer, including controlled randomized trials to develop standardized therapeutic protocols. In existing research, “significant differences in effects are observed based on concentration, cannabinoid type, and cancer type,” Caplan notes. “For example, THC can have both inhibitory and stimulatory effects on breast cancer cell proliferation depending on receptor activation pathways.” “Cannabinoids interact with multiple pathways, sometimes leading to unintended pro-tumor effects,” he writes. “The review suggests caution, as these mechanisms are not fully understood and require further exploration. Indeed, the endocannabinoid system may be one of the pivotal ‘drivers’ of physiology, but we have yet to determine which elements stimulate or inhibit its effects.” PDF of the review paper described: https://bit.ly/48g7qal

✨ Acidic pH at physiological salinity enhances the antitumor efficacy of lenvatinib, a drug targetting vascular endothelial growth factor receptors ✨ Our recent study demonstrates that acidic pH at physiological salinity significantly enhances the antitumor efficacy of lenvatinib, a drug targeting vascular endothelial growth factor receptors (VEGFR). By investigating the tumor microenvironment, we observed that acidic conditions, commonly found in the tumor extracellular matrix, improve lenvatinib’s ability to inhibit tumor growth. This discovery suggests that pH modulation may play a pivotal role in enhancing the pharmacodynamics of VEGFR-targeted therapies, potentially leading to more effective cancer treatment protocols. These findings could have profound implications for future oncology research and the development of combination therapies that optimize the tumor environment to increase drug efficacy.

Exploring pharmacokinetic variability of palbociclib in HR+/HER2- metastatic breast cancer: a focus on age, renal function, and drug–gene interactions Frontiers https://lnkd.in/g6NgiksF

September 2024, Prostate Cancer Awareness Month. 🔎 Prostate cancer is a major leading cause of cancer-related deaths in men with an incidence rate that is foreseen as increasing*. Although recent therapeutic advances have brought some relief, such as, for example, PARP inhibitors, androgen biosynthesis inhibitors, androgen receptor antagonists of second generation, many efforts still need to be made to achieve sustained disease control and long-term survival of patients with prostate cancer. There is an urgent need to characterize the many pathways that are involved in prostate cancer diseases. 🔬 At NovAliX, we provide an integrated offer from medicinal chemistry, in vitro pharmacology, relevant rodent in vivo pharmacology models to DMPK, translational science and histology solutions to support your projects throughout the drug discovery process. ▶️ Contact us to learn how we can support your discovery projects on cancer disease: https://lnkd.in/e9WnGYyQ *Figure source: https://lnkd.in/ecDzVQWi #drugdiscovery #pharmacology #medicinalchemistry #Cancer #ProstateCancer

The landscape of oncology is rapidly evolving with the advent of precision medicine. The FDA has sanctioned both gene- and immune-targeted medications for tissue-agnostic, genomic biomarker–driven indications in patients grappling with refractory solid tumors and hematologic malignancies. As the comprehension of the underlying science governing these cancers progresses, the roster of drugs authorized for tumors with genomic aberrations is expected to burgeon. Delve deeper into tissue-agnostic targeted therapies to unearth innovative treatments tailored to an individual's cancer, predicated on the specific genetic anomalies present in their tumor. Follow InviMeds Health to stay informed on the latest advancements and unique therapies tailored to individual genetic abnormalities, revolutionizing cancer care. #PrecisionMedicine #OncologyInnovation #TissueAgnosticTherapies #GenomicBiomarkers #CancerTreatment #InviMedsHealth #PersonalizedMedicine #PrecisionOncology #GeneticAbnormalities #ClinicalAdvancements #InviMedsHealth

Exciting news from Nandana lab! Our latest study, led by first author Sayanika Dutta, has just been published in Oncogene. Our study demonstrates that TBX2 functions as a molecular switch, mediating the transition from androgen receptor (AR) to glucocorticoid receptor (GR) signaling, thereby driving enzalutamide resistance. Notably, we provide critical insights into potential therapeutic strategies to effectively target and reverse this AR-to-GR signaling switch by disrupting TBX2-GR and TBX2-LSD1 protein-protein interactions. The translational significance of our findings is highlighted by the ongoing efforts to develop pharmaceuticals aimed at re-sensitizing castration resistant prostate cancer to androgen receptor signaling inhibitors. https://lnkd.in/g_JhsKJm

💕 "BREAKING---   😆 1st article in our SPECIAL ISSUE: "#Mechanisms of Targeted Therapy #Resistance and #ReversalStrategies" is out NOW! Don't miss the latest insights! #TargetedTherapy #ResistanceReversal #CancerResearch"   Academic Editor: Pier Paolo Piccaluga, University of Bologna, Italy    📚 In this review, authors describe the characteristics of TIS in breast cancer and detail the changes in phenotype that accompany its induction. We also discuss strategies for targeting senescent cancer cells in order to prevent or delay tumour recurrence.   🎬 Therapy-induced senescence in #BreastCancer: an overview   📝 Authors: Suraj Narayanan Chembukavu , Andrew J Lindsay *    🏃♂️ Welcome to read, forward, and share the article! https://lnkd.in/gxvth5Y2   #DrugResistance, therapy-induced senescence, #MembraneTrafficking, #IronMetabolism, #Senotherapeutics