turigrobart (LY3848575) / Eli Lilly - LARVOL DELTA

Systemic inflammation and prognosis in patients with RAS/BRAF wild-type metastatic colorectal cancer receiving anti-EGFR therapy: A real-world cohort study. (PubMed, Colorectal Dis) - "Routinely assessed markers of systemic inflammation are independently prognostic in patients with mCRC receiving anti-EGFR therapy and may serve as useful adjuncts in informing discussions with patients about prognosis."

Biomarker • Journal • Real-world evidence • Retrospective data • Colorectal Cancer • Oncology • Solid Tumor • BRAF • EREG

Interfollicular communication among preovulatory follicles after luteinizing hormone signaling. (PubMed, Endocrinology) - "Although epiregulin and amphiregulin are known to transmit LH signals within individual follicles, our findings indicate that they can also coordinate responses among neighboring follicles. Together, these results demonstrate that LH regulates a communication network between preovulatory follicles rather than acting solely at the level of individual follicles."

Journal • EGFR • EREG

DHODH inhibition drives albumin-mediated drug resistance through TERF2IP lactylation-activated macropinosome-mitochondria contact. (PubMed, Nat Commun) - "This metabolic shift promotes lysine 208 lactylation of telomeric repeat-binding factor 2-interacting protein (TERF2IP), unveiling its moonlighting function in transcriptional activation of epiregulin, which activates EGFR signaling to promote macropinocytosis...This adaptive response contributes to drug resistance in vitro and in vivo, and co-administration of DHODH inhibitors with macropinocytosis blockers or EGFR inhibitors enhances anti-tumor efficacy. Our findings reveal a previously unknown metabolic stress-induced macropinocytosis pathway and provide a rationale for combination therapy to enhance DHODH inhibitor efficacy in cancer treatment."

Journal • Oncology • EREG

Proliferation and differentiation in intestinal organoids are balanced by ligand-modulated EGFR trafficking. (PubMed, Life Sci Alliance) - "Addition of EGF or Epiregulin (EREG) triggered receptor endocytosis, reducing cell-surface levels and expression. While EGF promoted crypt proliferation, EREG promoted both proliferation and villus differentiation compared with untreated controls. Removal or re-introduction of EGF or EREG proved sufficient to induce development comparable to the constant presence of ligands over 96 h. Sub-saturating concentrations of EGF led to increased villus differentiation, resembling EREG treatments, suggesting that control over EGFR endocytic cycle regulates its plasma membrane localization shaping the balance of proliferation and differentiation in mSIOs."

Journal • Oncology • EGFR • EREG

Panitumumab-Based EGFR Blockade in SMARCB1-Deficient Renal Medullary Carcinoma: Preclinical Basis and Prospective Clinical Activity. (PubMed, Clin Cancer Res) - "Wild-type EGFR is a foundational dependency in RMC that is effectively targeted by panitumumab-based therapy. These findings, derived from a non-randomized registry, provide a biological and clinical rationale for further prospective validation."

Journal • Preclinical • Genito-urinary Cancer • Kidney Medullary Carcinoma • Oncology • Renal Cell Carcinoma • Solid Tumor • EGFR • EREG • LAMP1 • SMARCB1

A proteomic signature of oocyte quality from models of varying oocyte developmental competence. (PubMed, Hum Reprod) - "This study adds to the wider literature indicating that oocytes matured in vitro, either through CAPA-IVM or IVM, are unable to achieve the developmental competence rates observed with in vivo stimulation. Through examination of the global proteome in oocytes, molecular pathways including eukaryotic translation, autophagy, and endocytosis were dysregulated in in vitro oocytes. Recent findings have revealed the critical role of these pathways to developmental competence in the context of in vivo development. In cumulus cells, changes in reactive oxygen species detoxification and serine biosynthesis were observed, adding to the extensive knowledge around metabolic activity in cumulus cells as a critical facet of oocyte quality. Combined, these data suggest that the necessary processes of protein storage and degradation in oocytes and metabolism in cumulus cells constitute important components of oocyte quality. These processes appear suboptimal in current IVM systems,..."

Journal • EREG • PHGDH

Adenosine Receptor 3 Antagonism Suppresses Adipogenesis via the EREG-EGFR-Leptin Axis in Multipotent Cells. (PubMed, Biofactors) - "Transcriptomic profiling and pathway analysis performed in C3H10T1/2 cells suggested that the Ereg gene, which encodes epiregulin (EREG), is a potential target of MRS1220 mediated adipogenesis inhibition...In contrast, the AR3 agonist CF101 enhanced adipogenesis independent of the EREG-EGFR-leptin axis. These findings establish AR3 as a key regulator of adipogenic differentiation and uncover an AR3-EREG-EGFR-leptin signaling cascade as a mechanism by which AR3 antagonism inhibits adipogenesis. Targeting AR3 may offer a novel strategy to modulate adipose tissue formation in metabolic diseases."

Journal • Metabolic Disorders • EGFR • EREG • LEP • PPARG

Quiescent tumor cells shape the immunosuppressive microenvironment in pancreatic cancer. (PubMed, Nat Commun) - "These quiescent cells express high levels of Epiregulin (EREG), a secreted ligand for EGFR and ErbB4, and induce an immunosuppressive tumor microenvironment by increasing the frequency of ErbB4-expressing tumor-associated macrophages. Using complementary genetic and pharmacologic approaches, we demonstrate that targeting EREG enhances the sensitivity of quiescent tumor cells and PDAC tumors to CAR T-cell therapy, resulting in reduced relapse and improved overall survival. These findings support a model in which rare quiescent tumor cells contribute to remodeling of the PDAC tumor microenvironment through EREG-associated signaling and suggest that EREG inhibition may enhance the efficacy of adoptive cellular immunotherapy in this disease."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • EGFR • ERBB4 • EREG

Senescence Gene Expression Profiles and 90-Day Outcome in Stroke Patients. (PubMed, Neurology) - "Increased senescence was associated with worse stroke outcome. These findings suggest that blood cell senescence may contribute to vascular aging and worse stroke outcome, likely by altering epidermal growth factor receptor signaling, increasing inflammation and blood-brain barrier disruption. This study provides translational evidence that measuring senescence may reflect a biological aging process that influences functional outcome after stroke."

Journal • Cardiovascular • Diabetes • Inflammation • Ischemic stroke • Metabolic Disorders • Type 2 Diabetes Mellitus • EGFR • EREG

Effects of LY3848575 Versus Placebo in Participants With Painful Distal Sensory Polyneuropathy (clinicaltrials.gov) - P2 | N=558 | Completed | Sponsor: Eli Lilly and Company | Active, not recruiting ➔ Completed | Trial completion date: Sep 2026 ➔ Apr 2026 | Trial primary completion date: Jun 2026 ➔ Jan 2026

Trial completion • Trial completion date • Trial primary completion date • Neuralgia • Pain

J4F-MC-CYAB: Effects of LY3848575 Versus Placebo in Participants With Painful Distal Sensory Polyneuropathy (clinicaltrialsregister.eu) - P1/2 | N=67 | Completed | Sponsor: Eli Lilly & Co. | Active, not recruiting ➔ Completed

Trial completion • Neuralgia • Pain

Effects of LY3848575 Versus Placebo in Participants With Painful Distal Sensory Polyneuropathy (clinicaltrials.gov) - P2 | N=450 | Active, not recruiting | Sponsor: Eli Lilly and Company | Recruiting ➔ Active, not recruiting

Enrollment closed • Neuralgia • Pain

Effects of LY3848575 Versus Placebo in Participants With Painful Distal Sensory Polyneuropathy (clinicaltrials.gov) - P2 | N=450 | Recruiting | Sponsor: Eli Lilly and Company | Not yet recruiting ➔ Recruiting

Enrollment open • Neuralgia • Pain

Effects of LY3848575 Versus Placebo in Participants With Painful Distal Sensory Polyneuropathy (clinicaltrials.gov) - P2 | N=450 | Not yet recruiting | Sponsor: Eli Lilly and Company

New P2 trial • Neuralgia • Pain