Solid tumors have complex biology and structure comprising cancer cells, stromal cells, and the extracellular matrix. While most therapeutics target the cancer cells, recent data suggest that cancer cell behavior and response to treatment are markedly influenced by the tumor microenvironment (TME). In particular, the cancer-associated fibroblasts (CAFs) are the most abundant stromal cells, and play a significant contextual role in shaping tumor initiation, progression, and metastasis. CAFs have therefore emerged as part of the next-generation cancer drug design and discovery innovation strategy. We report here new findings on differential expression and prognostic significance of CAF markers in several cancers. We utilized two publicly available resources: The Cancer Genomic Atlas and Gene Expression Profiling Interactive Analysis. We examined the expression of CAF markers, ACTA2, S100A4, platelet-derived growth factor receptor-beta [PDGFR-β], CD10, and fibroblast activation protein-alpha (FAP-α), in tumor tissues versus the adjacent normal tissues. We found that CAF markers were differentially expressed in various different tumors such as colon, breast, and esophageal cancers and melanoma. No CAF marker is expressed in the same pattern in all cancers, however. Importantly, we report that patients with colon adenocarcinoma and esophageal carcinoma expressing high FAP-α and CD10, respectively, had significantly shorter overall survival, compared with those with low levels of these CAF markers (p < 0.05). We call for continued research on TME biology and clinical evaluation of the CAF markers ACTA2, S100A4, PDGFR-β, CD10, and FAP-α in relation to prognosis of solid cancers in large population samples. An effective cancer drug design and discovery roadmap in the 21st century ought to be broadly framed, and include molecular targets informed by both cancer cell and TME variations.

中文翻译：

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拓宽肿瘤微环境的药物设计和靶标？癌症中与癌症相关的成纤维细胞标记物表达与生存结果的相关性。

实体瘤具有复杂的生物学和结构，包括癌细胞，基质细胞和细胞外基质。尽管大多数治疗方法以癌细胞为靶标，但最新数据表明，癌细胞的行为和对治疗的反应受到肿瘤微环境（TME）的显着影响。尤其是，与癌症相关的成纤维细胞（CAF）是最丰富的基质细胞，在塑造肿瘤的发生，发展和转移方面起着重要的背景作用。因此，CAF已成为下一代癌症药物设计和发现创新策略的一部分。我们在这里报告了几种癌症中CAF标记的差异表达和预后意义的新发现。我们利用了两个可公开获得的资源：《癌症基因组图谱》和《基因表达谱分析互动分析》。在肿瘤组织中，与邻近的正常组织相比，ACTA2，S100A4，血小板衍生的生长因子受体-β[ PDGFR-β ]，CD10和成纤维细胞活化蛋白-α（FAP-α）。我们发现，CAF标志物在各种不同的肿瘤（例如结肠癌，乳腺癌，食道癌和黑色素瘤）中差异表达。但是，在所有癌症中，没有CAF标记以相同的模式表达。重要的是，我们报道了患者的结肠腺癌和食管癌高表达FAP-α和CD10，分别有显著总生存期，与那些与这些CAF标志物水平低（比较p <0.05）。我们呼吁继续进行TME生物学研究以及CAF标记ACTAA2，S100A4，PDGFR-β，CD10和FAP-α与大量人群中实体癌预后的临床评价。应该对21世纪有效的癌症药物设计和发现路线图进行概括，并包括受癌细胞和TME变化影响的分子靶标。