时间标签：数据日期 2026-11-05 · 生成时间 2026-11-05 05:30（Asia/Shanghai）｜ 检索窗口 PubMed edat 2026/11/02 – 2026/11/06 ｜ 情报发生日期 2026-11-05
研究问题
These adaptive programs preserve sufficient cellular fitness to allow the subsequent emergence and selection of more stable resistant states.The adaptive window hypothesis can be tested by asking whether therapeutic perturbations leave multiple viable adaptive trajectories accessible and whether candidate interventions reduce that accessibility.；Whether the accessibility of adaptive trajectories depends on shared permissive regulators, on context-specific and partially redundant networks, or emerges from distributed interactions among tumor and microenvironmental processes therefore remains unresolved.；Consequently, a single time point may capture a dominant adaptive state without establishing whether alternative viable trajectories remain accessible.
方法
We consider these processes as interconnected programs that shape melanoma evolution under treatment.Therapeutic agents are commonly regarded as cytotoxic or cytostatic interventions whose primary function is to eliminate tumor cells.；We conceptualize the adaptive window as a biologically defined and temporally dynamic phase during which tumors retain the capacity to access alternative viable adaptive trajectories under therapeutic pressure.；Whereas fixed resistance mechanisms vary substantially among patients and even among lesions from the same patient, early adaptive responses may converge on a more restricted set of biological processes and dependencies.
核心结论
Surviving cells instead remodel signaling, metabolism, transcription and interactions with the tumor microenvironment (TME), thereby maintaining sufficient viability under continued therapeutic pressure.Accumulating evidence indicates that such adaptive responses frequently precede genetically encoded resistance (8).；These findings illustrate that therapy-induced remodeling of a signaling node does not necessarily abolish critical downstream functions but may instead redistribute cellular dependencies and generate context-specific vulnerabilities.；RIPK1 therefore lies at the intersection of interferon-driven adaptation, TNF-dependent survival and inflammatory cell death, illustrating how sustained immune pressure can be converted into both tumor-cell survival and microenvironmental immunosuppression.Collectively, these nodes illustrate a broader principle: adaptation emerges through the reorganization of interconnected signaling networks rather than through the activation of isolated pathways.
局限
However, they also disrupt cellular homeostasis and trigger coordinated biological responses (7).；In vivo, however, neither perturbation occurs in isolation: melanoma cells integrate changes in intracellular signaling, metabolism, cytokine exposure, immune surveillance, extracellular matrix composition and nutrient availability, as described in this and in the following metabolic section and summarized in Figure 2.；Durable adaptation, however, requires the subsequent coordination of stress responses, inflammatory cues, metabolic remodeling and cell-state plasticity.2.2Adaptation to immune-mediated inflammatory pressureImmune-mediated inflammatory pressure represents a fundamentally distinct form of therapeutic stress.
对本项目的价值
中高价值：属「线粒体质量控制与氧化应激」方向；线粒体功能与氧化应激栏目可用作本项目文献库与综述素材。 ｜ 价值分 3.1/5（★★★☆☆）
全文来源
PubMed PMC JATS（正文 67,255 字符，题名指纹 0.91，已过 PubMed PMCID 官方关联 + 题名指纹 + 正文长度归属校验）
原文题录
- 中文题名：收窄适应窗口：约束黑色素瘤治疗耐药的免疫-代谢策略
- 英文标题：Closing the adaptive window: immune-metabolic strategies to constrain melanoma therapy resistance.
- 期刊与标识：Frontiers in immunology · PMID 42979158 · DOI 10.3389/fimmu.2026.1954638 · PMC PMC13728773