The non-receptor tyrosine kinase (TK) Src is the first oncogene ever identified. In tumors, Src hyperactivation is usually linked to the aberrant activation of upstream receptor tyrosine kinases (RTKs). In previous work, researchers from IRCCS-Fondazione Santa Lucia and collaborators developed a library of pyrazolo[3,4-d]pyrimidines inhibiting Src and other cytoplasmic TKs. Several compounds showed in vitro and in vivo activity in tumor models characterized by a deregulation of those kinases, such as osteosarcoma, neuroblastoma and glioblastoma.
A method for parallel sequencing of single-cell extrachromosomal circular DNA (ecDNA) and full-length mRNA transcriptomes has enabled new insights into the roles of ecDNA in cancer progression, researchers from Charité hospital and the Max Delbrück Center for Molecular Medicine reported in Nature Genetics on May 8, 2023. Circular DNAs are present in at least a third of cancer cells, and their presence correlates with poor prognosis in many cases. They can carry driver genes that have separated themselves from their chromosome of origin, and some research suggests that they serve as “reserve copies” of driver genes. Boundless Bio Inc. is in phase I trials targeting ecDNAs.
Neuroblastoma is among the deadliest cancers in infants, with frequent relapse and long-term survival being <10%. Recently, it has been found that protein RD3 is constitutively expressed in healthy adult and fetal tissues beyond the retina, and it follows a gradient expression from high to low levels in ganglioneuroma and neuroblastoma.
Over half of the children with high-risk neuroblastoma experience late relapses caused by minimal residual disease. Since chimeric antigen receptor (CAR) T-cell therapy has shown efficacy against minimal residual disease in pediatric patients with hematologic malignancies, several CAR T-cell therapies are being investigated for neuroblastoma.
Prazer Therapeutics Inc. has identified mitogen-activated protein kinase 14 (MAPK14) inhibitors reported to be useful for the treatment of inflammatory disorders.
Major histocompatibility complex class I (MHC-I) gene promoters are bivalently modified during development, which can be exploited in cancer cells to silence MHC-I expression and evade CD8+ T cells; in cells that exhibit bivalent modification of MHC-I genes, lower levels of cell surface MHC-I can be induced either by PRC2 inhibition or exposing the cells to interferon γ (IFNγ) in conjunction with polycomb inhibition to allow a permissive chromatin status.
Metacen Therapeutics Corp. has synthesized compounds able to capture methylglyoxal (MGO) reported to be useful for the treatment of aging, diabetes, hyperlipidemia, neurodegeneration, autism spectrum disorder, nonalcoholic fatty liver disease (NAFLD), fibrosis and cardiovascular disorders.
Sciclone Pharmaceuticals Holdings Ltd. has obtained marketing approval in China for Danyelza (naxitamab) for patients with relapsed or refractory high-risk neuroblastoma. The drug, in combination with granulocyte macrophage colony-stimulating factor, was approved to treat pediatric patients aged 1 and above, as well as adults, who have relapsed or refractory high-risk neuroblastoma in the bone or bone marrow and have demonstrated a partial or minor response to prior therapy or stable disease.
Sciclone Pharmaceuticals Holdings Ltd. has obtained marketing approval in China for Danyelza (naxitamab) for patients with relapsed or refractory high-risk neuroblastoma. The drug, in combination with granulocyte macrophage colony-stimulating factor, was approved to treat pediatric patients aged 1 and above, as well as adults, who have relapsed or refractory high-risk neuroblastoma in the bone or bone marrow and have demonstrated a partial or minor response to prior therapy or stable disease.
Following the tone set in an October U.S. FDA Oncologic Drugs Advisory Committee meeting, the agency has issued a complete response letter (CRL) to Y-mabs Therapeutics Inc.’s BLA for Omblastys (131I-omburtamab) to treat central nervous system/leptomeningeal metastasis arising from neuroblastoma.
