582 The discovery of new therapeutic combinations for Merkel cell carcinoma by small-molecule synergy screening

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

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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
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
CONCLUSION: irPR features are consistent across tumor types and treatment settings. Standardized, pan-tumor immune-mediated pathologic response criteria (irPRC) are defined and associated specimen-handling considerations are described. Future, prospective studies are merited to validate irPRC in larger datasets and to associate pathologic features with long-term patient outcomes. PMID: 31672770 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer that lacks durable responses to conventional chemotherapy. Some patients with MCC respond to immune checkpoint inhibitors (ICI), but many show disease progression despite immunotherapy. Patients with immunosuppression or autoimmunity may be precluded from using ICI at all. There are two categories of MCC: virus-positive MCC (VP-MCC) is characterized by integration of the Merkel cell polyomavirus into the host genome and represents the majority of cases, whereas virus-negative MCC (VN-MCC) is associated with mutations induced by ultraviolet light.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Pharmacology and Drug Development Source Type: research
AbstractMerkel cell carcinoma (MCC) is a rare but highly aggressive neuroendocrine skin cancer whose incidence has almost doubled in recent decades. Risk factors for MCC include age> 65  years, immunosuppression, sun exposure and infection by Merkel cell polyomavirus. MCC usually presents as rapidly growing, firm, red to violaceous nodule localized on the sun-exposed skin. Surgery followed by radiation therapy is considered to be the first-line treatment for primary or loco-region al MCC in order to prevent recurrences and lymph node metastasis, while chemotherapy has always been used to treat advanced forms. Howev...
Source: Dermatology and Therapy - Category: Dermatology Source Type: research
(Johns Hopkins Medicine) The first study of the immunotherapy drug pembrolizumab as the initial treatment for patients with a rare but aggressive form of skin cancer known as Merkel cell carcinoma reports better responses and longer survival than expected with conventional chemotherapy.
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news
This article discusses the use of avelumab for the treatment of mMCC and management of associated toxicities. METHODS: Literature on mMCC disease state and clinical trial data for avelumab were reviewed. FINDINGS: Avelumab has been investigated in patients with mMCC either following disease progression after one or more prior lines of chemotherapy or no prior systemic therapy. These patients experience clinically meaningful benefit. About 70% of patients receiving avelumab experience treatment-related adverse events. Given the limited benefit of chemotherapy, managing symptoms related to avelumab is key to admini...
Source: Clinical Journal of Oncology Nursing - Category: Nursing Authors: Tags: Clin J Oncol Nurs Source Type: research
This article synthetizes the actual clinical practice guidelines, the safety and efficacy data from the recent clinical trials and the on-going clinical trials to help clinicians in the treatment of MCC patients. PMID: 30579571 [PubMed - as supplied by publisher]
Source: Bulletin du Cancer - Category: Cancer & Oncology Authors: Tags: Bull Cancer Source Type: research
AbstractPurpose of ReviewSkin cancer is the most common malignancy in the USA, arising when mutated cells escape the host ’s natural immune surveillance. Immunotherapy helps boost the host’s immune system, augmenting the antitumor response. Given the ability of the immune system to evolve with a tumor’s evasive maneuvers, it is not surprising that immunotherapy has demonstrated durable clinical benefit in patient s with cancer, including certain types of skin cancers. Significant progress has been made with the recent development of immunotherapy for skin cancers.Recent FindingsHere, we review the literat...
Source: Current Dermatology Reports - Category: Dermatology Source Type: research
ConclusionsMCC disease was not perceived by the interviewed patients to result in severe functional limitations or to severely impact everyday activities, but was associated with substantial negative psychological impact. In contrast, chemotherapy and radiotherapy for MCC are highly debilitating and disrupt patients ’ lives.ClinicalTrials.gov identifierNCT02155647.
Source: The Patient - Patient-Centered Outcomes Research - Category: International Medicine & Public Health Source Type: research
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