Hida Tokimasa
Department of Dermatology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-Ku, Sapporo, 060-8543, Japan.
Int J Clin Oncol. 2025 May;30(5):856-866. doi: 10.1007/s10147-025-02755-9. Epub 2025 Mar 29.
Immune checkpoint inhibitors and molecular-targeted therapies have dominated recent cancer treatment. However, these treatments face challenges, such as primary and acquired resistance, indicating that not all patients benefit from them. Therefore, the search for new molecular targets is crucial. In addition, immune checkpoint inhibitors have exhibited racial differences in their effectiveness for certain neoplasms. Hence, understanding the genomic landscape of cancers in various racial groups is important. In Japan, health insurance has covered comprehensive genomic profiling since 2019, and the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) has accumulated genetic abnormalities along with clinical data of patients with various cancers. These data are crucial for advancing cancer research and drug development. This review discusses the genetic abnormalities of the major skin malignancies including melanoma, cutaneous squamous cell carcinoma (cSCC), and extramammary Paget's disease (EMPD), and proposes potential treatment strategies by comparing C-CAT data analysis with other genetic studies. The C-CAT data have emphasized unique genetic alterations in tumors of the Japanese population, particularly racial differences in tumor mutational burden in cutaneous melanoma and cSCC, indicating the importance of personalized treatment strategies that consider racial differences.
免疫检查点抑制剂和分子靶向疗法在近期的癌症治疗中占据了主导地位。然而,这些治疗面临着诸如原发性和获得性耐药等挑战,这表明并非所有患者都能从中受益。因此,寻找新的分子靶点至关重要。此外,免疫检查点抑制剂在某些肿瘤的疗效上表现出种族差异。因此,了解不同种族群体癌症的基因组格局很重要。在日本,自2019年以来,医疗保险已涵盖全面的基因组分析,癌症基因组学与先进治疗中心(C-CAT)积累了各种癌症患者的基因异常情况以及临床数据。这些数据对于推进癌症研究和药物开发至关重要。本综述讨论了包括黑色素瘤、皮肤鳞状细胞癌(cSCC)和乳腺外佩吉特病(EMPD)在内的主要皮肤恶性肿瘤的基因异常情况,并通过将C-CAT数据分析与其他基因研究进行比较,提出了潜在的治疗策略。C-CAT数据强调了日本人群肿瘤中独特的基因改变,特别是皮肤黑色素瘤和cSCC中肿瘤突变负担的种族差异,这表明考虑种族差异的个性化治疗策略的重要性。