Cancer Biology and Evolution Program, Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
Department of Cancer Physiology, Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
Cancer Control. 2020 Jul-Aug;27(3):1073274820945980. doi: 10.1177/1073274820945980.
Uniquely in nature, living systems must acquire, store, and act upon information. The survival and replicative fate of each normal cell in a multicellular organism is determined solely by information obtained from its surrounding tissue. In contrast, cancer cells as single-cell eukaryotes live in a disrupted, heterogeneous environment with opportunities and hazards. Thus, cancer cells, unlike normal somatic cells, must constantly obtain information from their environment to ensure survival and proliferation. In this study, we build upon a simple mathematical modeling framework developed to predict (1) how information promotes population persistence in a highly heterogeneous environment and (2) how disruption of information resulting from habitat fragmentation increases the probability of population extinction. Because (1) tumors grow in a highly heterogeneous microenvironment and (2) many cancer therapies fragment tumors into isolated, small cancer cell populations, we identify parallels between these 2 systems and develop ideas for cancer cure based on lessons gleaned from Anthropocene extinctions. In many Anthropocene extinctions, such as that of the North American heath hen (), a large and widespread population was initially reduced and fragmented owing to overexploitation by humans (a "first strike"). After this, the small surviving populations are vulnerable to extinction from environmental or demographic stochastic disturbances (a "second strike"). Following this analogy, after a tumor is fragmented into small populations of isolated cancer cells by an initial therapy, additional treatment can be applied with the intent of extinction (cure). Disrupting a cancer cell's ability to acquire and use information in a heterogeneous environment may be an important tactic for causing extinction following an effective initial therapy. Thus, information, from the scale of cells within tumors to that of species within ecosystems, can be used to identify vulnerabilities to extinction and opportunities for novel treatment strategies.
在自然界中，生命体必须获取、存储和处理信息。多细胞生物中每个正常细胞的生存和复制命运仅取决于其周围组织获得的信息。相比之下，作为单细胞真核生物的癌细胞生活在一个紊乱、异质的环境中，充满了机遇和危险。因此，与正常体细胞不同，癌细胞必须不断从环境中获取信息以确保生存和增殖。在这项研究中，我们基于一个简单的数学建模框架，该框架旨在预测：(1) 信息如何促进高度异质环境中的种群持续存在；(2) 由于栖息地破碎化导致的信息中断如何增加种群灭绝的概率。由于：(1) 肿瘤在高度异质的微环境中生长；(2) 许多癌症疗法将肿瘤分割成孤立的小癌细胞群体，我们发现这两个系统之间存在相似之处，并根据从人类世灭绝中吸取的经验教训为癌症治疗提出了思路。在许多人类世灭绝中，如北美林莺 () 的灭绝，最初由于人类的过度开发导致一个庞大而广泛的种群减少和破碎化（一次打击）。在此之后，幸存的小种群容易受到环境或人口随机干扰的灭绝威胁（二次打击）。根据这一类比，在初始治疗将肿瘤分割成小的孤立癌细胞群体后，可以应用额外的治疗方法，意图是灭绝（治愈）。在异质环境中破坏癌细胞获取和使用信息的能力，可能是在有效初始治疗后导致灭绝的重要策略。因此，信息可以从肿瘤内细胞的规模扩展到生态系统内物种的规模，用于识别灭绝的脆弱性和新治疗策略的机会。
