The crosstalk between oncogenic signaling and ferroptosis in cancer

Pang, Qianghu; Tang, Zhirou; Luo, Lianxiang

doi:10.1016/j.critrevonc.2024.104349

Cited by 4 publications

(1 citation statement)

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“…For a long time, apoptosis was considered the major programmed cell-death pathway in cells exposed to cytotoxic agents. Recently the existence of other cell-death pathways like ferroptosis, necroptosis, pyroptosis, parthanatos, and PANoptosis have gained prominence in cancer research [ 12 , 13 , 14 , 15 , 16 ]. Anti-GD2 mouse monoclonal antibody 14G2a was shown to induce direct cell cytotoxicity in certain NB cell lines [ 17 ], but the analysis was restricted to apoptosis as this was the major cell-death pathway known at that time.…”

Section: Introductionmentioning

confidence: 99%

Hu14.18K.322A Causes Direct Cell Cytotoxicity and Synergizes with Induction Chemotherapy in High-Risk Neuroblastoma

Thomas,

Nguyen,

Drnevich

et al. 2024

Cancers

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The disialoganglioside, GD2, is a promising therapeutic target due to its overexpression in certain tumors, particularly neuroblastoma (NB), with limited expression in normal tissues. Despite progress, the intricate mechanisms of action and the full spectrum of the direct cellular responses to anti-GD2 antibodies remain incompletely understood. In this study, we examined the direct cytotoxic effects of the humanized anti-GD2 antibody hu14.18K322A (hu14) on NB cell lines, by exploring the associated cell-death pathways. Additionally, we assessed the synergy between hu14 and conventional induction chemotherapy drugs. Our results revealed that hu14 treatment induced direct cytotoxic effects in CHLA15 and SK-N-BE1 cell lines, with a pronounced impact on proliferation and colony formation. Apoptosis emerged as the predominant cell-death pathway triggered by hu14. Furthermore, we saw a reduction in GD2 surface expression in response to hu14 treatment. Hu14 demonstrated synergy with induction chemotherapy drugs with alterations in GD2 expression. Our comprehensive investigation provides valuable insights into the multifaceted effects of hu14 on NB cells, shedding light on its direct cytotoxicity, cell-death pathways, and interactions with induction chemotherapy drugs. This study contributes to the evolving understanding of anti-GD2 antibody therapy and its potential synergies with conventional treatments in the context of NB.

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