Scientific and clinical developments in Merkel cell carcinoma: A polyomavirus-driven, often-lethal skin cancer.
Scientific and clinical developments in Merkel cell carcinoma: A polyomavirus-driven, often-lethal skin cancer.
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DOI：
10.1016/j.jdermsci.2021.10.004
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发表时间：
2022-01
影响因子：
4.6
通讯作者：
Nghiem P
中科院分区：
文献类型：
--
作者：
Akaike T;Nghiem P
默克尔细胞癌（MCC）是一种原发性神经内分泌皮肤癌，约40%的病例会复发。默克尔细胞多瘤病毒（MCPyV）和紫外线（UV）诱导的突变是MCC的两个主要致病因素。病毒阳性MCC表达具有高度免疫原性但又是持续肿瘤生长所需的多瘤病毒癌蛋白。病毒阴性MCC具有编码肿瘤特异性UV-新抗原的UV-DNA突变的高负荷。因此，紫外线和病毒诱导的MCC都具有高度免疫原性，能够实现多种T细胞靶向治疗。最佳MCC管理是具有挑战性的，因为它的罕见性，侵袭性，快速发展的护理指南，以及与其他皮肤癌相比管理的根本差异。MCC通常通过广泛的手术，放疗或全身治疗进行积极管理，经常导致可能可以避免的毒性，同时仍然实现最佳的疾病控制。因此，多学科护理对于为患者提供最佳结果至关重要。由于PD-1通路阻断剂为相当一部分MCC患者提供了持久的获益，许多晚期MCC患者的前景在过去十年中取得了显著进展。早期MCC的管理也得到了改善，这是由于更好的方法来整合手术和放疗。由于分期特异性复发数据和复杂的“液体活检”可以早期发现疾病复发，因此预后准确性和持续监测已经取得了进展。在这里，我们总结了最近的显着进展和紧迫的挑战，如PD-（L）1难治性MCC，MCC患者的免疫功能障碍的管理。我们还强调了各种资源，使供应商能够利用这一快速发展领域的最新进展。
Merkel cell carcinoma (MCC) is a primary neuroendocrine skin cancer that recurs in ~40% of cases. Merkel cell polyomavirus (MCPyV) and ultraviolet (UV)-induced mutations are two major causative factors of MCC. Virus-positive MCCs express polyomavirus oncoproteins that are highly immunogenic yet are required for ongoing tumor growth. Virus-negative MCCs have a high burden of UV-DNA mutations that encode tumor-specific UV-neoantigens. Thus, both UV-and virus-induced MCCs are highly immunogenic, enabling diverse T-cell targeted therapies. Optimal MCC management is challenging given its rarity, aggressive nature, rapidly evolving care guidelines, and fundamental differences in management compared to other skin cancers. MCC is often managed aggressively with extensive surgery, radiotherapy or systemic therapy, frequently leading to toxicities that might have been avoidable while still achieving optimal disease control. Thus, multi-disciplinary care is crucial for providing patients with the best possible outcomes. The outlook for many patients with advanced MCC has progressed remarkably over the past decade due to PD-1 pathway blocking agents that provide durable benefit for a substantial subset of MCC patients. The management of early-stage MCC has also improved due to better approaches to integrate surgery and radiotherapy. Prognostic accuracy and ongoing surveillance have advanced due to stage-specific recurrence data and sophisticated “liquid biopsies” that allow early detection of disease recurrence. Here we summarize both recent striking progress and pressing challenges such as PD-(L)1-refractory MCC, and management of MCC patients with immune dysfunction. We also highlight diverse resources to allow providers to take advantage of recent progress in this fast-moving field.
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DOI：
10.1111/bjd.19150
发表时间：
2021-03
期刊：
The British journal of dermatology
影响因子：
--
作者：
Akaike T;Qazi J;Anderson A;Behnia FS;Shinohara MM;Akaike G;Hippe DS;Thomas H;Takagishi SR;Lachance K;Park SY;Tarabadkar ES;Iyer JG;Blom A;Parvathaneni U;Vesselle H;Nghiem P;Bhatia S
通讯作者：
Bhatia S
DOI：
10.1016/s1470-2045(16)30364-3
发表时间：
2016-10
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Kaufman HL;Russell J;Hamid O;Bhatia S;Terheyden P;D'Angelo SP;Shih KC;Lebbé C;Linette GP;Milella M;Brownell I;Lewis KD;Lorch JH;Chin K;Mahnke L;von Heydebreck A;Cuillerot JM;Nghiem P
通讯作者：
Nghiem P
影响因子：
10.9
作者：
Nghiem P;Bhatia S;Lipson EJ;Sharfman WH;Kudchadkar RR;Brohl AS;Friedlander PA;Daud A;Kluger HM;Reddy SA;Boulmay BC;Riker A;Burgess MA;Hanks BA;Olencki T;Kendra K;Church C;Akaike T;Ramchurren N;Shinohara MM;Salim B;Taube JM;Jensen E;Kalabis M;Fling SP;Homet Moreno B;Sharon E;Cheever MA;Topalian SL
通讯作者：
Topalian SL
影响因子：
4
作者：
Iyer JG;Parvathaneni U;Gooley T;Miller NJ;Markowitz E;Blom A;Lewis CW;Doumani RF;Parvathaneni K;Anderson A;Bestick A;Liao J;Kane G;Bhatia S;Paulson K;Nghiem P
通讯作者：
Nghiem P
影响因子：
28.4
作者：
D'Angelo, Sandra P.;Russell, Jeffery;Kaufman, Howard L.
通讯作者：
Kaufman, Howard L.