Department of Medical Biology, Centre Scientifique de Monaco (CSM), MC, Monaco.
Trev and Joyce Deeley Research Centre, BC Cancer, Victoria, BC, Canada.
Adv Exp Med Biol. 2021;1301:7-24. doi: 10.1007/978-3-030-62026-4_2.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal cancers with a dismal 5-year survival rate of 5% and very limited efficacy of the current therapeutic regimens. The lethality of PDAC stems from asymptomatic early stage of the disease, its propensity to rapidly disseminate, as well as unusual, dense and highly active surrounding stroma. Fortunately, promising literature data suggests that exploiting newly contextualized type of cell death, termed "ferroptosis", has great potential for overcoming the major problems regarding PDAC treatment. A major player in this type of cell death is Glutamate/Cystine antiporter - xCT, which is responsible for the uptake of oxidized form of cysteine, and thus maintenance of intracellular amino acid and redox homeostasis. xCT seems to fulfill all requirements of the solid and specific molecular target for ferroptosis-based anti-cancer therapy. In this chapter we summarized mounting literature data supporting this hypothesis, but also, we pointed out some of the underexamined aspects of xCT-dependent (patho)physiology of the cancer cell, which have to be addressed in future studies. The abstract could be used as "informative abstract" for the online version.
胰腺导管腺癌（PDAC）是最具侵袭性和致命性的癌症之一，其 5 年生存率仅为 5%，目前的治疗方案疗效非常有限。PDAC 的致命性源于疾病的无症状早期阶段、其快速扩散的倾向以及异常、密集和高度活跃的周围基质。幸运的是，有前景的文献数据表明，利用新的细胞死亡类型，即“铁死亡”，具有克服 PDAC 治疗主要问题的巨大潜力。这种细胞死亡的主要参与者是谷氨酸/胱氨酸转运蛋白 - xCT，它负责摄取氧化形式的半胱氨酸，从而维持细胞内氨基酸和氧化还原平衡。xCT 似乎满足了基于铁死亡的抗癌治疗的固体和特定分子靶标的所有要求。在这一章中，我们总结了支持这一假设的越来越多的文献数据，但我们也指出了一些尚未充分研究的 xCT 依赖性（病理）癌症细胞生理学方面，这些方面必须在未来的研究中得到解决。摘要可用于在线版本的“信息性摘要”。
