Therapeutic Challenges in Targeting Cell Death

Submission Deadline: 30 April 2025 View: 62 Submit to Special Issue

Guest Editors

Prof. Dr. Godefridus J Peters

Email: gj.peters@amsterdamumc.nl; gj.peters@gumed.edu.pl

Affiliation: 1. Laboratory Medical Oncology, Cancer Center Amsterdam, AmsterdamUMC. PO Box 7057, 1007 MB Amsterdam

2. Department of Biochemistry, Medical University of Gdansk, Debinki 1, 80—211 Gdansk, Poland

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Research Interests: Drug mEtabolism and Transport, Cell desath mechanisms, drug devvelopment, pharmacology

Prof. Dr. Frank A.E.Kruyt

Email: f.a.e.kruyt@umcg.nl

Affiliation: Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands

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Research Interests: cell death mechanisms, apoptosis, lung cancer, gliomas

Summary

Cells can die through various molecular mechanisms. Traditionally, cell death was categorized into necrosis and apoptosis, with the latter being referred to as programmed cell death. Programmed cell death plays a significant role in conventional chemotherapy and radiotherapy sensitivity, but it has become evident that these, along with other cell death mechanisms, are also crucial to the efficacy of protein kinase inhibitors (including tyrosine kinase inhibitors) and immunotherapy.

Advances in understanding the intrinsic and extrinsic apoptotic pathways, as well as their cross-talk, have facilitated the targeting of apoptosis in cancer therapy. Several specific inhibitors of apoptosis have been developed, including small molecules (MW <500) directed at apoptosis inhibitory proteins and agonistic antibodies or recombinant proteins against cell death receptors such as TRAIL receptors. These compounds are often more effective when used in combination with conventional DNA-targeted drugs, other apoptosis inhibitors, radiation, and/or immunotherapy.

Recent developments have highlighted the roles of specialized cell death mechanisms such as ferroptosis and cuproptosis. Ferroptosis is a regulated form of death driven by iron-dependent phospholipid peroxidation, while cuproptosis results from copper overload, leading to mitochondrial dysfunction. Increasing evidence links both ferroptosis and cuproptosis to cancer initiation, growth, and metastasis. Pharmacological induction of ferroptosis or cuproptosis could offer novel strategies for targeting specific tumors or drug-resistant cancer cells. Another form of programmed cell death is pyroptosis, which is independent of caspase activation and distinct from both apoptosis and necrosis.

The evolving understanding of both traditional and novel apoptotic pathways has led to the development of innovative cancer therapies, including small molecules, nanolipids, and PROTACs. This Special Issue on “Therapeutic Challenges in Targeting Cell Death” aims to feature Original Articles, Reviews, and Commentaries that focus on these novel therapeutic developments for both solid and hematological malignancies.

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