Clear cell renal cell carcinoma (ccRCC) is the most prevalent subtype of renal cancer, accounting for approximately 80% of all renal cell cancers. Due to its exceptional inter- and intratumor heterogeneity, it is highly resistant to conventional systemic therapies. Targeting the evasion of cell death, one of cancer's hallmarks, is currently emerging as an alternative strategy for ccRCC. In this article, we review the current state of apoptosis-inducing therapies against ccRCC, including antisense oligonucleotides, BH3 mimetics, histone deacetylase inhibitors, cyclin-kinase inhibitors, inhibitors of apoptosis protein antagonists, and monoclonal antibodies. Although preclinical studies have shown encouraging results, these compounds fail to improve patients' outcomes significantly. Current evidence suggests that inducing apoptosis in ccRCC may promote tumor progression through apoptosis-induced proliferation, anastasis, and apoptosis-induced nuclear expulsion. Therefore, re-evaluating this approach is expected to enable successful preclinical-to-clinical translation.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2024 May 22 [Epub ahead of print]
Adam Kowalewski, Jędrzej Borowczak, Mateusz Maniewski, Karol Gostomczyk, Dariusz Grzanka, Łukasz Szylberg
Department of Tumor Pathology and Pathomorphology, Oncology Centre Prof. Franciszek Łukaszczyk Memorial Hospital, Bydgoszcz 85-796, Poland; Center of Medical Sciences, University of Science and Technology, Bydgoszcz 85-796, Poland. Electronic address: ., Clinical Department of Oncology, Oncology Centre Prof. Franciszek Łukaszczyk Memorial Hospital, Bydgoszcz 85-796, Poland., Department of Tumor Pathology and Pathomorphology, Oncology Centre Prof. Franciszek Łukaszczyk Memorial Hospital, Bydgoszcz 85-796, Poland; Doctoral School of Medical and Health Sciences, Nicolaus Copernicus University in Torun, Bydgoszcz 85-094, Poland., Department of Obstetrics, Gynaecology and Oncology, Chair of Pathomorphology and Clinical Placentology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz 85-094, Poland., Department of Clinical Pathomorphology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz 85-094, Poland., Department of Tumor Pathology and Pathomorphology, Oncology Centre Prof. Franciszek Łukaszczyk Memorial Hospital, Bydgoszcz 85-796, Poland; Department of Obstetrics, Gynaecology and Oncology, Chair of Pathomorphology and Clinical Placentology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz 85-094, Poland.