Regulated Necrotic Cell Death in Alternative Tumor Therapeutic Strategies

Abstract

The treatment of tumors requires the induction of cell death. Radiotherapy, chemotherapy, and immunotherapy are administered to kill cancer cells; however, some cancer cells are resistant to these therapies. Therefore, effective treatments require various strategies for the induction of cell death. Regulated cell death (RCD) is systematically controlled by intracellular signaling proteins. Apoptosis and autophagy are types of RCD that are morphologically different from necrosis, while necroptosis, pyroptosis, and ferroptosis are morphologically similar to necrosis. Unlike necrosis, regulated necrotic cell death (RNCD) is caused by disruption of the plasma membrane under the control of specific proteins and induces tissue inflammation. Various types of RNCD, such as necroptosis, pyroptosis, and ferroptosis, have been used as therapeutic strategies against various tumor types. In this review, the mechanisms of necroptosis, pyroptosis, and ferroptosis are described in detail, and a potential effective treatment strategy to increase the anticancer effects on apoptosis- or autophagy-resistant tumor types through the induction of RNCD is suggested.

Current and Future Therapies for Immunogenic Cell Death and Related Molecules to Potentially Cure Primary Breast Cancer

“…Various anticancer agents induce cellular modalities, including apoptosis, autophagy, and necrosis [ 14 ]. Apoptosis is generally associated with cell turnover under physiological conditions.…”

A novel pyroptosis-related lncRNA signature for prognostic prediction in patients with lung adenocarcinoma

“…The typical pyroptotic pathway is sparked by the activation of nucleotide-binding domain leucine-rich repeats family protein 3 (NLRP3) inflammasomes as well as the associated inflammatory response [13,14]. Several reports have verified that pyroptosis plays a critical role in tumorigenesis and cancer treatment [15][16][17][18][19]. Notably, various cancers, including colon cancer [20,21], gastric cancer [22], hepatocellular carcinoma [23,24], breast cancer [25,26] and lung cancer [27,28], are sensitive to pyroptosis.…”

Immunogenic Cell Death Induction by Ionizing Radiation

“…As a form of RCD, necroptosis is mediated by receptor-interacting serine/threonine-protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like protein (MLKL), and leads to cellular swelling, membrane disruption, and intracellular contents release ( 54 , 55 ). The successful induction of necroptosis with IR in non-small cell lung cancer (NSCLC) cells depends on irradiation dose, fractionation schedule, and RIPK3 expression.…”