Elia Ilaria, Schmieder Roberta, Christen Stefan, Fendt Sarah-Maria
Vesalius Research Center, VIB, 3000, Leuven, Belgium.
Department of Oncology, KU Leuven, 3000, Leuven, Belgium.
Handb Exp Pharmacol. 2016;233:321-53. doi: 10.1007/164_2015_10.
Targeting cancer metabolism has the potential to lead to major advances in tumor therapy. Numerous promising metabolic drug targets have been identified. Yet, it has emerged that there is no singular metabolism that defines the oncogenic state of the cell. Rather, the metabolism of cancer cells is a function of the requirements of a tumor. Hence, the tissue of origin, the (epi)genetic drivers, the aberrant signaling, and the microenvironment all together define these metabolic requirements. In this chapter we discuss in light of (epi)genetic, signaling, and environmental factors the diversity in cancer metabolism based on triple-negative and estrogen receptor-positive breast cancer, early- and late-stage prostate cancer, and liver cancer. These types of cancer all display distinct and partially opposing metabolic behaviors (e.g., Warburg versus reverse Warburg metabolism). Yet, for each of the cancers, their distinct metabolism supports the oncogenic phenotype. Finally, we will assess the therapeutic potential of metabolism based on the concepts of metabolic normalization and metabolic depletion.
靶向癌症代谢有可能在肿瘤治疗方面取得重大进展。众多有前景的代谢药物靶点已被确定。然而，现已发现不存在单一的代谢方式能定义细胞的致癌状态。相反，癌细胞的代谢是肿瘤需求的一种函数。因此，肿瘤的起源组织、（表观）遗传驱动因素、异常信号传导以及微环境共同决定了这些代谢需求。在本章中，我们将根据（表观）遗传、信号传导和环境因素，探讨基于三阴性乳腺癌和雌激素受体阳性乳腺癌、早期和晚期前列腺癌以及肝癌的癌症代谢多样性。这些癌症类型都表现出独特且部分相反的代谢行为（例如，瓦伯格效应与逆瓦伯格代谢）。然而，对于每种癌症而言，其独特的代谢都支持致癌表型。最后，我们将基于代谢正常化和代谢耗竭的概念评估代谢的治疗潜力。
