The use of mimicking antibodies that activate death receptors (DRs) to selectively induce cell death in cancer cells has shown limited clinical success so far, primarily due to suboptimal efficacy and safety concerns, particularly hepatotoxicity. Emerging strategies to enhance efficacy include the development of bispecific antibodies that simultaneously target DRs and tumor-specific antigens.
The transcriptional repressor B-cell lymphoma 6 (BCL6) plays a central role in the development and progression of various B-cell malignancies, particularly diffuse large B-cell lymphoma (DLBCL), where it is associated with poor prognosis and resistance to standard immunochemotherapy.
Targeted protein degradation has yet to notch its first approval. But with more than two dozen agents now in clinical trials, the strategy’s ultimate clinical validation appears to be a matter of time.
Multiple myeloma (MM) is a complex disease with poor prognosis and its clinical management still remains a challenge in the field. Since both BCMA and GPRC5D are overexpressed in MM cells, a therapeutic approach targeting both would be of interest. Qilu Pharmaceutical Co. Ltd. is hence developing a dual BCMA- and GPRC5D-targeting antibody – QLS-4131 – for the treatment of MM.
SMARCA4 and SMARCA2 are essential subunits of the SWI/SNF complex, functioning as ATP-dependent chromatin remodelers that regulate gene expression and maintain cellular homeostasis. Recent research has shown that selectively targeting SMARCA2 is an effective cancer treatment strategy, with several compounds already in early clinical testing.
HER3 overexpression in solid tumors is tied to poor prognosis, concretely in breast and non-small-cell lung cancers, where treatment resistance often occurs upon using targeted therapy, highlighting the need for novel targeted therapies against HER3. Since its expression is much higher in tumor than normal cells, HER3 is a robust candidate for antibody-drug conjugate (ADC) therapy.
“I think we’ve come a long way in understanding the importance of this biology. We know it affects men and women, children and adults,” Paul Mischel told the audience during his plenary talk at the 2025 Annual Meeting of the American Association for Cancer Research (AACR 2025). “It’s very prevalent, it’s very devastating. It creates resistance. And we’ve learned some very fundamental rules about this biology that are driving it.”
Neuroblastoma, an aggressive malignancy originating from neural crest cells, accounts for 15% of cancer-related deaths in children. Treatment strategies include systemic chemotherapy, radiation or immunotherapy with anti-GD2 antibodies, all with severe side effects and long-term toxicity. Retinoic acid (RA) has been shown to promote neuroblastoma growth inhibition while suppressing MYCN oncogene expression. However, its effect is reversible, and tumor regrowth may occur.
Researchers from Vicero Inc. have developed a Vincobody platform, which allows for design of novel proprietary VHH antibody fragments that possess the efficacy of dual checkpoint blockade while mitigating the toxicity limitations of current monoclonal antibody therapies.
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