The last 50 years have witnessed extraordinary developments in understanding mechanisms of carcinogenesis, synthesized as the hallmarks of cancer. Despite this logical framework, our understanding of the molecular basis of systemic manifestations and the underlying causes of cancer-related death remains incomplete. Looking forward, elucidating how tumors interact with distant organs and how multifaceted environmental and physiological parameters impinge on tumors and their hosts will be crucial for advances in preventing and more effectively treating human cancers. In this perspective, we discuss complexities of cancer as a systemic disease, including tumor initiation and promotion, tumor micro- and immune macro-environments, aging, metabolism and obesity, cancer cachexia, circadian rhythms, nervous system interactions, tumor-related thrombosis, and the microbiome. Model systems incorporating human genetic variation will be essential to decipher the mechanistic basis of these phenomena and unravel gene-environment interactions, providing a modern synthesis of molecular oncology that is primed to prevent cancers and improve patient quality of life and cancer outcomes.
在过去的五十年里，我们对癌症发生机制的认识取得了显著进展，这些成果被归纳为癌症的特征。尽管已有这一逻辑框架，我们对癌症全身性表现的分子基础及其导致死亡的根本原因的理解仍不完整。展望未来，阐明肿瘤如何与远处器官相互作用，以及多方面的环境和生理参数如何影响肿瘤及其宿主，对于预防和更有效治疗人类癌症的进展至关重要。本文从系统性疾病的角度探讨癌症的复杂性，涵盖肿瘤发生与促进、肿瘤微环境和免疫大环境、衰老、代谢与肥胖、癌症恶病质、昼夜节律、神经系统交互作用、肿瘤相关血栓形成以及微生物组。整合人类遗传变异的研究模型将对于揭示这些现象的机制基础、解析基因-环境互作至关重要，从而构建现代分子肿瘤学的综合框架，为预防癌症、改善患者生活质量和治疗结局奠定基础。
肿瘤(癌症)患者之家