Oncology Frontier: Could you please summarize recent progress in clinical and basic research on new molecular-targeted therapies against peripheral T-cell lymphoma?
《肿瘤瞭望》:请您总结下目前外周T细胞淋巴瘤分子靶向治疗临床及基础研究进展。
Dr Piccaluga: In the last five to ten years, we have made progress in the knowledge of the biology of the tumor. In particular, we have added evidence that some molecules can be targeted with new drugs. Some of these can be targeted with tyrosine kinases and our group demonstrated a few years ago that platelet-derived growth factor receptors are expressed by most peripheral T-cell lymphomas and that the signaling of such receptors is required for tumor proliferation and possibly survival of the tumor cells. So clinical trials testing tyrosine kinase inhibitors are ongoing. More evidence from the biology of the tumors reveals that epigenetic rather than genetic abnormalities are a main feature of peripheral T-cell lymphoma biology and different drugs targeting the epigenome are under evaluation. One of these, romidepsin, has already been approved for the treatment of relapsed patients, and others are close to being approved in Europe and the US. Although not biological breakthrough, because we have known for a long time that CD30 is expressed in some T-cell lymphomas, the development of an efficient anti-CD30 conjugated antibody was a major improvement in the treatment of anaplastic large cell lymphomas. So those are the main improvements bridging biology to treatment in this field.
Piccaluga教授:在过去的五到十年间,我们在肿瘤分子生物学方面取得了很大进展,尤其是我们发现了一些分子的新靶向药物,其中一些为酪氨酸激酶靶向抑制剂。我们的研究发现,大多数外周T细胞淋巴瘤表达血小板衍生的生长因子受体,这些受体介导的信号转导途径是肿瘤增殖所必需的,也可能是肿瘤细胞存活所必需的。因此,检测酪氨酸激酶抑制剂的临床试验正在进行中。
另一方面,肿瘤分子生物学研究揭示了外周T细胞淋巴瘤的一个主要分子生物学特征是表观遗传异常而非基因异常,表观基因组的不同靶向药物也处于研究中。其中一个代表性药物罗米地辛,已在欧洲和美国被批准用于外周T细胞淋巴瘤复发患者的治疗,其他的相关药物也即将被批准使用。此外,一种有效的抗CD30结合抗体的发现虽然不是生物学上的突破,但已成为间变性大细胞淋巴瘤治疗的一大进步。综上所述,这些临床及基础研究是外周T细胞淋巴瘤分子靶向治疗取得进展的重要桥梁。