PARP inhibitors have been approved for the treatment of several cancers, including ovarian, breast, pancreatic and prostate cancers with BRCA mutations or other homologous recombination repair deficiencies (HRD). However, their therapeutic potential is limited by challenges such as hematologic toxicity and lack of target selectivity.
Programmed cell death protein 1 (PD-1) and vascular endothelial growth factor (VEGF) are often co-expressed in the tumor microenvironment. The combination of anti-PD-1 and anti-VEGF agents has been evaluated in patients with advanced non-small-cell lung cancer, with promising results from agents like ivonescimab, a PD-1/VEGF bispecific antibody.
Astrazeneca plc recently reported new preclinical data regarding their KRAS G12D inhibitor AZD-0022, currently in phase I/II clinical studies. The company presented the pharmacokinetic and pharmacodynamic profiling of the compound with the aim to push forward with its clinical development.
The leucine-rich repeat-containing protein 15 (LRRC15) is a cell surface protein involved in cell-cell and cell-matrix interactions, with limited expression in normal tissues.
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.
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