The Genomic Landscape of Merkel Cell Carcinoma and Clinicogenomic Biomarkers of Response to Immune Checkpoint Inhibitor Therapy.

The Genomic Landscape of Merkel Cell Carcinoma and Clinicogenomic Biomarkers of Response to Immune Checkpoint Inhibitor Therapy. Clin Cancer Res. 2019 Aug 09;: Authors: Knepper TC, Montesion M, Russell J, Sokol ES, Frampton GM, Miller VA, Albacker LA, McLeod HL, Eroglu Z, Khushalani NI, Sondak VK, Messina JL, Schell MJ, DeCaprio JA, Tsai KY, Brohl AS Abstract PURPOSE: Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy which has demonstrated sensitivity to immune checkpoint inhibitor therapy. Here, we perform the largest genomics study in MCC to date to characterize the molecular landscape and evaluate for clinical and molecular correlates to immune checkpoint inhibitor response. EXPERIMENTAL DESIGN: Comprehensive molecular profiling was performed on 317 tumors from patients with MCC including the evaluation of oncogenic mutations, tumor mutational burden (TMB), mutational signatures, and the Merkel Cell Polyomavirus (MCPyV). For a subset of 57 patients, a retrospective analysis was conducted to evaluate for clinical and molecular correlates to immune checkpoint inhibitor response and disease survival. RESULTS: Genomic analyses revealed a bimodal distribution in TMB, with two molecularly distinct subgroups. 94% (n=110) of TMB-high specimens exhibited an ultraviolet light (UV) mutational signature. MCPyV genomic DNA sequences were not identified in any TMB-high cases (0/117), but were in 63% (110/175) of TMB-low cases. For 36 ...
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research

Related Links:

Merkel cell carcinoma (MCC) is a rare, highly aggressive skin cancer for which immune modulation by immune checkpoint inhibitors show remarkable response rates. However, primary or secondary resistance to immunotherapy prevents benefits in a significant proportion of patients. For MCC, one immune escape mechanism is insufficient recognition by T cells due to downregulation of major histocompatibility complex (MHC) class I surface expression. Histone deacetylase (HDAC) inhibitors have been demonstrated to epigenetically reverse low MHC class I expression caused by downregulation of the antigen processing machinery (APM).
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Original Article Source Type: research
This article reviews the most current literature on the surgical and medical management of MCC.
Source: Archives of Dermatological Research - Category: Dermatology Source Type: research
Conclusions: SSA could be a valid therapeutic option in patients with MCC with high SR expression. When combined with PD-1/PD-L1 immune-checkpoint inhibition, SSA is likely to enhance antiproliferative activity. Our case report provides the rationale to conduct a prospective trial and translational research to verify the efficacy and safety of combined SSA and checkpoint inhibitors for advanced MCC.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In this report, a group of experts of the Spanish Society of Medical Oncology (SEOM), the Spanish Society of Medical Radiology (SERAM), and Spanish Society of Nuclear Medicine and Molecular Imaging (SEMNIM) provide an up-to-date review and a consensus guide on these issues. PMID: 32623581 [PubMed - as supplied by publisher]
Source: Clinical Genitourinary Cancer - Category: Cancer & Oncology Authors: Tags: Clin Transl Oncol Source Type: research
Merkel cell carcinoma (MCC) is a rare and highly metastatic neuroendocrine skin cancer. The majority of MCC tumors are virus positive (VP-MCC) and are associated with integrated Merkel cell polyomavirus, whereas the remainder of MCC are virus-negative (VN-MCC) tumors that are characterized by ultraviolet light associated mutations. Metastatic MCC is treated by immunotherapy or chemotherapy. Conventional chemotherapy is usually unbeneficial in MCC, and although immune checkpoint inhibitor (ICI) therapy can be effective, it is contraindicated in many patients and others have disease progression despite immunotherapy.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Pharmacology and Drug Development Source Type: research
Merkel cell carcinoma (MCC) is an aggressive skin cancer that often recurs. MCC tumors can respond to PD-1 pathway inhibitors rapidly, however, it is unclear how often these responses persist after discontinuation of therapy. We retrospectively assessed 159 persons with advanced MCC treated with first-line anti-PD-(L)1 agents. Non-responders were defined as those with progressive disease (PD) or stable disease (SD), while responders had partial response (PR), or complete response (CR), based on clinician assessment.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Translational Studies Source Type: research
arma Terry A. Day Cancers that arise in the head and neck region are comprised of a heterogeneous group of malignancies that include carcinogen- and human papillomavirus (HPV)-driven mucosal squamous cell carcinoma as well as skin cancers such as cutaneous squamous cell carcinoma, basal cell carcinoma, melanoma, and Merkel cell carcinoma. These malignancies develop in critical areas for eating, talking, and breathing and are associated with substantial morbidity and mortality despite advances in treatment. Understanding of advances in the management of these various cancers is important for all multidisciplinary prov...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
AbstractSkin cancers remain the most common group of cancers globally, and the incidence continues to rise. Although localized skin cancers tend to have excellent outcomes following surgical excisions, the less common cases that become surgically unresectable or metastatic have been associated with poor prognosis and suboptimal treatment responses to cytotoxic chemotherapy. Development of monoclonal antibodies to programmed cell death-1 receptor and its ligand (PD-1/PD-L1) have transformed the management of metastatic melanoma, squamous cell carcinoma, and Merkel cell carcinoma. These agents, as monotherapies, are associat...
Source: BioDrugs - Category: Drugs & Pharmacology Source Type: research
In this study, we reviewed the real-world data on different treatments given to MCC patients in Finland in 1986–2016. We used the Finnish Cancer Registry database to find MCC patients and the Hospital Discharge Register and the Cause-of-Death Register to obtain treatment data. We identified 376 MCC patients and 33 different treatment entities and/or combinations of treatment. An increase was noted in the incidence of MCC since 2005. Therefore, the cohort was divided into two groups: the “early“ group with time of diagnosis between years 1986 and 2004 and the “late” group wi...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
This report presents key information on the basis for the Food and Drug Administration's accelerated approval of pembrolizumab for the treatment of recurrent locally advanced or metastatic Merkel cell carcinoma, including efficacy and safety information. This approval provides patients and physicians with an additional treatment option for this aggressive and life-threatening carcinoma. PMID: 32272501 [PubMed - as supplied by publisher]
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Oncologist Source Type: research
More News: Cancer | Cancer & Oncology | Carcinoma | Immunotherapy | Merkel Cell Carcinoma | Study