Conley et al show that such an initiative is indeed feasible, at least in terms of gathering appropriate clinical data and tissue samples from more than 100 eligible cases. As noted, whole-exome sequencing and other molecular studies have been performed on these samples, the results of which will be reported elsewhere. However, recent advances in genomic analyses of tumors suggest such an approach may prove successful. For example, combined tumor and germline multigene DNA sequencing has found an unexpectantly high number of mutations in BRCA1, BRCA2, and other homologous-recombination genes in prostate and pancreatic cancers, leading to demonstrated activity of agents targeting these DNA repair pathways, such as platinums and PARP-inhibitors. High levels of microsatellite instability, known to confer sensitivity to PD-1 inhibitors in Lynch syndrome-associated colon and endometrial cancers, also occur in a small subset of most other cancers and predict for immunotherapy responses. These examples and many case reports suggest that the reverse process, discovering rare genetic predictors to cancer therapies through analyses of exceptional responders, may be feasible.
Conley等人表明，這樣的倡議確實是可行的，至少在從符合條件的100多個患者中收集適當的臨床數據和組織樣本方面是可行的。如上所述，已經對這些樣本進行全外顯子組測序和其他分子機制研究，其結果將在別處報導。然而，腫瘤基因組分析的最新進展表明，這種方法可能是有效的。例如，結合腫瘤和生殖系多基因DNA測序，在前列腺癌和胰腺癌中發現BRCA1、BRCA2和其他同源重組基因存在大量突變，從而證明靶向DNA修復途徑的藥物的活性，如鉑和PARP抑制劑。高水平微衛星不穩定現象，在與Lynch症候群相關的結腸癌和子宮內膜癌中使人增加對PD-1抑制劑敏感性，也出現在大多數其他癌症的一小部分患者中，並可藉此預測免疫治療效果。這些例子和許多病例報告表明，通過對療效超好的患者的分析發現癌症治療中罕見的癌基因預測因子的反向過程可能是可行的。
A recent perspective on exceptional responders contains a number of recommendations that may enhance future studies with similar objectives. Among them, and as noted in this article, is a comparison of the data from such responders with those from individuals with poor outcomes undergoing the same treatment.
關於療效超好的患者的最新觀點包含了一些建議，這些建議可能會對具有類似靶向分子進行深入的研究。正如本文所指出的，其中一項建議是將這些療效超好患者的數據與接受相同治療預後差的個體的數據進行比較。
Given the tremendous complexity of factors involved in tumor responses, among which are epigenetic, immunological, and host factors, it will take truly large-scale efforts to more broadly define additional characteristics contributing to exceptional responses. Ultimately, prospective studies of tumors from exceptional responders, particularly to novel, genomically targeted agents, may provide a powerful approach to cancer treatment discoveries.
鑑於腫瘤機制涉及的因素極其複雜，其中包括表觀遺傳因素、免疫學因素和宿主因素，要更廣泛地定義引起療效超好的其他因素，還需要大量的努力。最終，對療效超好的患者，尤其是接受新型的基因組靶向藥物的患者，進行腫瘤組織的前瞻性研究，可能為研究癌症的治療提供強有力的方法。
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