Grzywa Tomasz M, Paskal Wiktor, Włodarski Paweł K
The Department of Histology and Embryology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Banacha 1b, 02-091 Warsaw, Poland.
The Department of Histology and Embryology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Banacha 1b, 02-091 Warsaw, Poland.
Transl Oncol. 2017 Dec;10(6):956-975. doi: 10.1016/j.tranon.2017.09.007. Epub 2017 Oct 24.
Melanoma is a cancer that exhibits one of the most aggressive and heterogeneous features. The incidence rate escalates. A high number of clones harboring various mutations contribute to an exceptional level of intratumor heterogeneity of melanoma. It also refers to metastases which may originate from different subclones of primary lesion. Such component of the neoplasm biology is termed intertumor and intratumor heterogeneity. These levels of tumor heterogeneity hinder accurate diagnosis and effective treatment. The increasing number of research on the topic reflects the need for understanding limitation or failure of contemporary therapies. Majority of analyses concentrate on mutations in cancer-related genes. Novel high-throughput techniques reveal even higher degree of variations within a lesion. Consolidation of theories and researches indicates new routes for treatment options such as targets for immunotherapy. The demand for personalized approach in melanoma treatment requires extensive knowledge on intratumor and intertumor heterogeneity on the level of genome, transcriptome/proteome, and epigenome. Thus, achievements in exploration of melanoma variety are described in details. Particularly, the issue of tumor heterogeneity or homogeneity given BRAF mutations is discussed.
黑色素瘤是一种具有最具侵袭性和异质性特征之一的癌症。其发病率不断上升。大量携带各种突变的克隆导致黑色素瘤肿瘤内异质性达到异常水平。它还指可能起源于原发性病变不同亚克隆的转移灶。肿瘤生物学的这一组成部分被称为肿瘤间和肿瘤内异质性。这些肿瘤异质性水平阻碍了准确的诊断和有效的治疗。对该主题的研究数量不断增加,反映出需要了解当代疗法的局限性或失败原因。大多数分析集中在癌症相关基因的突变上。新型高通量技术揭示了病变内更高程度的变异。理论和研究的整合为免疫治疗靶点等治疗选择指明了新途径。黑色素瘤治疗中个性化方法的需求需要在基因组、转录组/蛋白质组和表观基因组水平上对肿瘤内和肿瘤间异质性有广泛的了解。因此,将详细描述黑色素瘤多样性探索方面的成果。特别是,将讨论给定BRAF突变情况下肿瘤异质性或同质性的问题。