Major European pharmaceutical companies are conducting extensive preclinical research to identify and validate new drug targets and biomarkers across various cancer types. This early stage research is crucial to inform clinical development of novel oncology therapies. This article summarizes recent advances from preclinical studies reported by 9 leading European pharma companies.
Sanofi researchers characterized an IgE antibody targeting the melanoma-associated antigen chondroitin sulfate proteoglycan 4 (CSPG4). In preclinical melanoma models, the antibody stimulated pro-inflammatory effects through activating myeloid cells and CD8+ T cells, providing a rationale for targeting CSPG4.
In preclinical models of BRCA-deficient cancers like ovarian and pancreatic, Sanofi found that inhibiting polymerase theta activated innate immunity through the cGAS-STING pathway. Combining a polymerase theta inhibitor with PD-1 blockade showed synergistic antitumor effects.
GlaxoSmithKline demonstrated that inhibiting protein arginine methyltransferase 5 (PRMT5) cooperated with the PARP inhibitor niraparib to impede DNA damage repair in preclinical models of breast and ovarian cancer . The combination synergistically reduced cancer cell viability.
In immunocompromised mouse strains used for patient-derived cancer xenografts, GlaxoSmithKline researchers characterized early-onset neurodegeneration marked by reactive astrocytes and microgliosis This finding could impact interpretation of xenograft studies.
Analyzing the RNA-binding protein landscape in the mouse brain, Novo Nordisk found that RBM5 was dysregulated in Huntington’s disease models. Since RBM5 controls neuronal processes, its disruption may contribute to Huntington’s pathogenesis.
Novo Nordisk researchers reported that in multiple myeloma bone pain models, sensory nerves sprout into periosteal and marrow tumor areas highly expressing nociceptive markers like CGRP. This study provides insight into mechanisms of myeloma-induced bone pain.
Lanthio Pharma developed LP2, an engineered cyclic angiotensin 1-7 analog, as a novel colorectal cancer therapy. In patient-derived xenograft models, LP2 impaired tumor growth and PI3K/AKT/mTOR signaling compared to standard EGFR inhibitors.
SIRION Biotech designed a modified syncytin-1 vaccine that boosted T and B cell responses against this endogenous retroviral envelope protein in mouse studies. Syncytin-1 is implicated in breast cancer and multiple sclerosis.
In cervical cancer models, SIRION Biotech showed that combining their E6E7 therapeutic vaccine ISA101 with cisplatin improved control of HPV-positive tumors. The vaccine also synergized with cisplatin to increase CD4+ and CD8+ T cell infiltration.
BerGenBio reported that in lung cancer models, loss of function of the tumor suppressor STK11 activated AXL signaling. This observation provides a rationale for targeting AXL in STK11-deficient cancers like KRAS-mutant lung tumors.
AstraZeneca developed an antibody-drug conjugate targeting B7-H3, which was highly expressed on treatment-resistant prostate cancers in preclinical models. B7-H3 expression correlated with neuroendocrine transdifferentiation and aggressive phenotypes.
In models of ER-positive breast cancer, AstraZeneca showed that combining the AKT inhibitor capivasertib and the SERD fulvestrant overcame palbociclib resistance. The combination reduced tumor growth and AKT/PI3K pathway activity.
AstraZeneca also reported that combining PD-L1 and CD73 blockade with radiotherapy augmented immunologic tumor control in pancreatic cancer models. The triple combination strategy stimulated T cell immunity and IFNγ production.
Cellectis engineered UCART20x22, a dual CAR T-cell therapy targeting CD20 and CD22, which displayed anti-tumor activity against mantle cell lymphoma and chronic lymphocytic leukemia in mouse models. UCART20x22 could help prevent antigen escape.
In separate work, Cellectis showed that arming CAR T cells with IL-15 and IL-7 helped overcome stromal barriers and enhanced efficacy against solid tumors like mesothelioma in preclinical studies. This novel approach warrants clinical evaluation.
In summary, European pharma preclinical research is uncovering new therapeutic opportunities and strategies against cancer. Continued investment into translational science and emerging technologies will be key to identify and validate the next generation of oncology targets and treatments.
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