Chen Yubin, Lin Pao-Hwa, Freedland Stephen J, Chi Jen-Tsan
Department of Molecular Genetics and Microbiology, Duke University, Durham, NC 27708, USA.
Center of Applied Genomic Technologies, Duke University, Durham, NC 27708, USA.
Cancers (Basel). 2024 May 24;16(11):1991. doi: 10.3390/cancers16111991.
Prostate cancer (PC) stands as the most frequently diagnosed non-skin cancer and ranks as the second highest cause of cancer-related deaths among men in the United States. For those facing non-metastatic PC necessitating intervention, solely local treatments may not suffice, leading to a possible transition toward systemic therapies, including androgen deprivation therapy (ADT), chemotherapy, and therapies targeting androgen. Yet, these systemic treatments often bring about considerable adverse effects. Additionally, it is observed that overweight men are at a higher risk of developing aggressive forms of PC, advancing to metastatic stages, and succumbing to the disease. Consequently, there is a pressing demand for new treatment options that carry fewer side effects and enhance the current standard treatments, particularly for the majority of American men who are overweight or obese. In this article, we will review the metabolic response to ADT and how lifestyle modulation can mitigate these ADT-associated metabolic responses with a particular focus on the two clinical trials, Carbohydrate and Prostate Study 1 (CAPS1) and Carbohydrate and Prostate Study 2 (CAPS2), which tested the effects of low-carbohydrate diets on the metabolic side effects of ADT and PC progression, respectively. Furthermore, we will summarize the findings of serum metabolomic studies to elucidate the potential mechanisms by which ADT and low-carbohydrate diets can affect the metabolic response to mitigate the metabolic side effects while maximizing therapeutic efficacy.
前列腺癌(PC)是最常被诊断出的非皮肤癌,在美国男性癌症相关死亡原因中排名第二。对于那些面临需要干预的非转移性PC患者,仅局部治疗可能不够,可能会转向全身治疗,包括雄激素剥夺疗法(ADT)、化疗和靶向雄激素的疗法。然而,这些全身治疗往往会带来相当大的副作用。此外,观察到超重男性患侵袭性PC、发展到转移阶段并死于该疾病的风险更高。因此,迫切需要副作用更少且能改进当前标准治疗的新治疗选择,特别是对于大多数超重或肥胖的美国男性。在本文中,我们将回顾对ADT的代谢反应,以及生活方式调节如何减轻这些与ADT相关的代谢反应,特别关注两项临床试验,即碳水化合物与前列腺研究1(CAPS1)和碳水化合物与前列腺研究2(CAPS2),它们分别测试了低碳水化合物饮食对ADT代谢副作用和PC进展的影响。此外,我们将总结血清代谢组学研究的结果,以阐明ADT和低碳水化合物饮食影响代谢反应以减轻代谢副作用同时最大化治疗效果的潜在机制。