Reactive Oxygen Species: A Promising Therapeutic Target for SDHx-Mutated Pheochromocytoma and Paraganglioma

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F21%3A00549246" target="_blank" >RIV/86652036:_____/21:00549246 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.mdpi.com/2072-6694/13/15/3769" target="_blank" >https://www.mdpi.com/2072-6694/13/15/3769</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/cancers13153769" target="_blank" >10.3390/cancers13153769</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Reactive Oxygen Species: A Promising Therapeutic Target for SDHx-Mutated Pheochromocytoma and Paraganglioma

Popis výsledku v původním jazyce

Simple Summary Pheochromocytoma and paraganglioma are rare neuroendocrine tumors that arise from chromaffin cells of the adrenal medulla or their neural crest progenitors located outside the adrenal gland, respectively. About 10-15% of patients develop metastatic disease for whom treatment options and availability are extremely limited. The risk of developing metastatic disease is increased for patients with mutations in succinate dehydrogenase subunit B, which leads to metabolic reprogramming and redox imbalance. From this perspective, we focus on redox imbalance caused by this mutation and explore potential opportunities to therapeutically target reactive oxygen species production in these rare tumors. Pheochromocytoma (PHEO) and paraganglioma (PGL) are rare neuroendocrine tumors derived from neural crest cells. Germline variants in approximately 20 PHEO/PGL susceptibility genes are found in about 40% of patients, half of which are found in the genes that encode succinate dehydrogenase (SDH). Patients with SDH subunit B (SDHB)-mutated PHEO/PGL exhibit a higher likelihood of developing metastatic disease, which can be partially explained by the metabolic cell reprogramming and redox imbalance caused by the mutation. Reactive oxygen species (ROS) are highly reactive molecules involved in a multitude of important signaling pathways. A moderate level of ROS production can help regulate cellular physiology, however, an excessive level of oxidative stress can lead to tumorigenic processes including stimulation of growth factor-dependent pathways and the induction of genetic instability. Tumor cells effectively exploit antioxidant enzymes in order to protect themselves against harmful intracellular ROS accumulation, which highlights the essential balance between ROS production and scavenging. Exploiting ROS accumulation can be used as a possible therapeutic strategy in ROS-scavenging tumor cells. Here, we focus on the role of ROS production in PHEO and PGL, predominantly in SDHB-mutated cases. We discuss potential strategies and approaches to anticancer therapies by enhancing ROS production in these difficult-to-treat tumors.

Název v anglickém jazyce

Reactive Oxygen Species: A Promising Therapeutic Target for SDHx-Mutated Pheochromocytoma and Paraganglioma

Popis výsledku anglicky

Simple Summary Pheochromocytoma and paraganglioma are rare neuroendocrine tumors that arise from chromaffin cells of the adrenal medulla or their neural crest progenitors located outside the adrenal gland, respectively. About 10-15% of patients develop metastatic disease for whom treatment options and availability are extremely limited. The risk of developing metastatic disease is increased for patients with mutations in succinate dehydrogenase subunit B, which leads to metabolic reprogramming and redox imbalance. From this perspective, we focus on redox imbalance caused by this mutation and explore potential opportunities to therapeutically target reactive oxygen species production in these rare tumors. Pheochromocytoma (PHEO) and paraganglioma (PGL) are rare neuroendocrine tumors derived from neural crest cells. Germline variants in approximately 20 PHEO/PGL susceptibility genes are found in about 40% of patients, half of which are found in the genes that encode succinate dehydrogenase (SDH). Patients with SDH subunit B (SDHB)-mutated PHEO/PGL exhibit a higher likelihood of developing metastatic disease, which can be partially explained by the metabolic cell reprogramming and redox imbalance caused by the mutation. Reactive oxygen species (ROS) are highly reactive molecules involved in a multitude of important signaling pathways. A moderate level of ROS production can help regulate cellular physiology, however, an excessive level of oxidative stress can lead to tumorigenic processes including stimulation of growth factor-dependent pathways and the induction of genetic instability. Tumor cells effectively exploit antioxidant enzymes in order to protect themselves against harmful intracellular ROS accumulation, which highlights the essential balance between ROS production and scavenging. Exploiting ROS accumulation can be used as a possible therapeutic strategy in ROS-scavenging tumor cells. Here, we focus on the role of ROS production in PHEO and PGL, predominantly in SDHB-mutated cases. We discuss potential strategies and approaches to anticancer therapies by enhancing ROS production in these difficult-to-treat tumors.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Cancers (Basel)

ISSN

2072-6694

e-ISSN

2072-6694

Svazek periodika

13

Číslo periodika v rámci svazku

15

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

9

Strana od-do

3769

Kód UT WoS článku

000681923600001

EID výsledku v databázi Scopus

2-s2.0-85111161129