Alkaliptosis: a new weapon for cancer therapy

Liu, Jiao; Kuang, Feimei; Kang, Rui; Tang, Daolin

doi:10.1038/s41417-019-0134-6

Cited by 70 publications

(49 citation statements)

References 34 publications

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“… 1 The traditional core types of cancer treatment are surgery, chemo‐therapy, and radiation therapy, which can reduce tumor cell proliferation by inducing cancer cell death. 2 However, accumulating evidence has shown that tumors often relapse and it has been suggested that successful oncotherapy requires prolonged antineoplastic immunity. 3 The field of cancer immunotherapy (CIT) has emerged in recent years and aims to stimulate the body's immune system to create a robust immune response that can kill cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Pyroptosis, a new bridge to tumor immunity

et al. 2021

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Environmental factors and genetic mutation have caused cancer incidence and mortality to rapidly increase. Cancer has become one of the crucial causes of death worldwide, and is becoming a major public health problem. 1 The traditional core types of cancer treatment are surgery, chemo-therapy, and radiation therapy, which can reduce tumor cell proliferation by inducing cancer cell death. 2 However, accumulating evidence has shown that tumors often relapse and it has been suggested that successful oncotherapy requires prolonged antineoplastic immunity. 3 The field of cancer immunotherapy (CIT) has emerged in recent years and aims to stimulate the body's immune system to create a robust immune response that can kill cancer cells. 4 This type of treatment can induce immunogenic cell death in different ways and achieve long-term anticancer immunity. 5 Although the application of CIT has been considered for a broad range of tumors, only a minority of patients achieve a satisfactory treatment effect due to immune escape. These results indicate that the immune system is intricate and still not well managed. 6 Thus, it is necessary to explore the mechanisms involved in CIT to develop more efficient methods of treatment for better cancer prevention and treatment.

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Section: Introductionmentioning

confidence: 99%

Pyroptosis, a new bridge to tumor immunity

et al. 2021

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“…Recently, iron-dependent regulated cell death (RCD), namely, ferroptosis, has drawn increasing attention in the cellular-molecular field of tumours. Less than a decade ago, ferroptosis was introduced as a nonapoptotic RCD distinguished from necroptosis [7], pyroptosis [8], and alkaliptosis [9,10]. In 2012, Dixon et al [11] first demonstrated that in contrast to apoptotic inhibitors, the growth inhibitory effect of erastin on RASmutant cancer cells can be completely antagonized by iron chelators and lipophilic antioxidants relying on a new form of RCD named ferroptosis.…”

Section: Introductionmentioning

confidence: 99%

A novel ferroptosis-related 12-gene signature predicts clinical prognosis and reveals immune relevancy in clear cell renal cell carcinoma

Hong

Lin

et al. 2021

BMC Cancer

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Background Clear cell renal cell carcinoma (ccRCC) is still highly aggressive and lethal even with various therapeutic approaches. As the kidney is an iron metabolism-related organ, exploring and assessing the clinical value of ferroptosis, an iron-dependent regulated cell death, is practical and important. Methods Prognostic ferroptosis-related differentially expressed genes (DEGs) were identified from the KIRC cohort in the cancer genome atlas (TCGA) database, from which a prognostic signature was established using Lasso-penalized Cox regression analysis. Each patient in the KIRC cohort and the E-MTAB-1980 cohort (from the ArrayExpress database) was assigned a calculated signature-correlated risk score and categorized to be either in the high- or low-risk group divided by the median risk score in the KIRC cohort. Then, the independent prognostic value of the signature was further assessed by Kaplan-Meier (K-M) survival, time-dependent receiver operating characteristic (ROC) and Cox regression analyses based on overall survival (OS) in both cohorts. Finally, risk-related DEGs were identified in both cohorts and subjected to enrichment analyses for Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and immune infiltration. Results Among 60 ferroptosis-related genes, 32 prognostic DEGs were identified, from which we constructed a prognostic 12-gene signature with CARS1, HMGCR, CHAC1, GOT1, CD44, STEAP3, AKR1C1, CBS, DPP4, FANCD2, SLC1A5 and NCOA4. Patients in both cohorts were divided into high- and low-risk groups, which were visually distributed in two sets and had positive-risk-related mortality. The K-M survival and the ROC curves validated that the signature has prognostic value with P < 0.05 and area under the curve > 0.7 in both cohorts, respectively. Multivariate Cox regression further confirmed the risk score as an independent prognostic predictor for OS. Commonly enriched terms in GO and KEGG not only showed a high iron correlation but also, interestingly, immune relevance of 3 immune cells (macrophages, mast cells and regulatory T cells) and 1 immune-related function (antigen processing cell co-stimulation). Conclusion We established a novel 12 ferroptosis-related-gene signature that was proven to be an independent prognostic predictor for OS and inferred to be related to tumour immunity in ccRCC; however, the underlying mechanism is still poorly characterized and needs further exploration.

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“…RCD can be further classified into apoptotic and nonapoptotic cell death that shows different morphological, genetic, and biochemical characteristics [5]. Since resistance to apoptosis is one of the main obstacles to the successful treatment of cancer, there has been a great interest in the development of reagents to trigger various forms of nonapoptotic cell death (e.g., necroptosis [6,7], pyroptosis [8,9], ferroptosis [10,11], alkaliptosis [12,13], and parthanatos [14,15]) to suppress tumor growth. However, similar to the results previously observed in conventional chemotherapy to induce apoptosis, tumor cells still have resistance to targeted nonapoptotic cell death.…”

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confidence: 99%

ESCRT-III-mediated membrane repair in cell death and tumor resistance

2020

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The plasma membrane is made of glycerophospholipids that separate the inner and outer parts of the cell. Under physiological conditions, it acts as a barrier and gatekeeper to protect cells from the environment. In pathological situations, it undergoes structural and functional changes, resulting in cell damage. Indeed, plasma membrane damage caused by various stresses (e.g., hypoxia, nutritional deficiencies, ultraviolet radiation, and chemotherapeutic agents) is one of the hallmarks of cell death. Phosphatidylserine exposure and plasma membrane blebbing usually occurs in apoptotic cells, while necrotic cells lose the integrity of the plasma membrane and thereby release intracellular damage-associated molecular patterns. In contrast, the endosomal sorting complex required for transport-III (ESCRT-III), an evolutionarily conserved protein complex with membrane fission machinery, plays a key role in the repair of damaged plasma membranes in various types of regulated cell death, such as necroptosis, pyroptosis, and ferroptosis. These emerging findings indicate that ESCRT-III is a potential target to overcome drug resistance during tumor therapy.

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Alkaliptosis: a new weapon for cancer therapy

Cited by 70 publications

References 34 publications

Pyroptosis, a new bridge to tumor immunity

Pyroptosis, a new bridge to tumor immunity

A novel ferroptosis-related 12-gene signature predicts clinical prognosis and reveals immune relevancy in clear cell renal cell carcinoma

ESCRT-III-mediated membrane repair in cell death and tumor resistance

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