Division of Dermatology, Department of Medicine, McGill University, Montreal, Canada
Division of Dermatology, Department of Medicine, McGill University, Montreal, Canada.
Life Sci Alliance. 2021 May 10;4(7). doi: 10.26508/lsa.202000651. Print 2021 Jul.
Basal cell carcinoma (BCC) is the most common skin cancer and human malignancy. Although most BCCs are easily managed, some are aggressive locally, require Mohs micrographic surgery, or can even metastasize. In the latter, resistance to Sonic Hedgehog inhibitors may occur. Despite their frequent occurrence in clinical practice, their transcriptional landscape remains poorly understood. By analyzing BCC RNA sequencing data according to clinically important features (all BCCs versus normal skin, high-risk versus low-risk BCCs based solely on histopathological subtypes with aggressive features, advanced versus non-advanced BCCs, and vismodegib-resistant versus vismodegib-sensitive tumors), we have identified novel differentially regulated genes and new targetable pathways implicated in BCC tumorigenesis. Pathways as diverse as , , , cadherins, integrins, , and β are promising therapeutic avenues for local and systemic agents in managing this common malignancy, including through drug re-purposing of existing medications. We experimentally validated several of these targets as biomarkers in our patient-derived cohort of primary BCC tumors.
基底细胞癌（BCC）是最常见的皮肤癌和人类恶性肿瘤。尽管大多数 BCC 易于治疗，但有些肿瘤具有局部侵袭性，需要 Mohs 显微外科手术治疗，甚至可能转移。在后者中，可能会出现对 Sonic Hedgehog 抑制剂的耐药性。尽管它们在临床实践中经常发生，但它们的转录景观仍知之甚少。通过根据临床重要特征（所有 BCC 与正常皮肤、仅根据具有侵袭性特征的组织病理学亚型进行高风险与低风险 BCC 分类、晚期与非晚期 BCC 以及维莫德吉耐药与维莫德吉敏感肿瘤）分析 BCC RNA 测序数据，我们已经确定了新的差异调控基因和新的可靶向途径，这些途径与 BCC 肿瘤发生有关。各种途径，如 Wnt、Notch、Hedgehog、钙黏着蛋白、整合素、PI3K-Akt 和 MAPK，为局部和全身药物管理这种常见的恶性肿瘤提供了有前途的治疗途径，包括通过重新利用现有药物进行药物再利用。我们在我们的患者衍生的原发性 BCC 肿瘤队列中实验验证了其中几个作为生物标志物的靶点。
