Discovery of 4 subtypes of melanoma points to new treatment approaches

FINDINGSMelanoma, a relatively rare but deadly skin cancer, has been shown to switch differentiation states — that is, to regress to an earlier stage of development — which can lead it to become resistant to treatment. Now, UCLA researchers have found that melanomas can be divided into four distinct subtypes according to their stages of differentiation. Cell subtypes that de-differentiated — meaning that they reverted back to a less-mature cell — showed sensitivity to a type of self-inflicted cell death called ferroptosis.The research also showed that certain subtypes of melanoma cells could be successfully treated using multiple cancer therapies in combination with ferroptosis-inducing drugs.BACKGROUNDMelanoma arises from melanocytes, cells that produce pigments. Although targeted therapies and a greater understanding of cancer immunology have significantly improved survival, many patients either relapse or do not respond to treatment.METHODThe UCLA team, led by Dr. Thomas Graeber, analyzed the gene expressions of melanoma cells and compared them to information in public genetics databases to identify the four different subtypes of melanoma  with different drug sensitivities. The team organized the melanoma cells according to characteristic patterns of genes they had turned on. Comparing the gene expression patterns to data from stem cells induced to differentiate to melanocytes, they discovered that melanomas can be found in four dif ferent diff...
Source: UCLA Newsroom: Health Sciences - Category: Universities & Medical Training Source Type: news

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Conditions:   Melanoma;   Cervical Carcinoma;   Pancreatic Carcinoma;   Triple Negative Breast Cancer;   Hepatocellular Carcinoma;   Urothelial Carcinoma;   Squamous Cell Carcinoma of the Head and Neck;   Nasopharyngeal Carcinoma;   Renal Cell Carcinoma;   Colorectal Carcinoma;   E ndometrial Carcinoma;   Non-small Cell Lung Carcinoma;   Small Cell Lung Carcinoma;   Gastric or Gastroesophageal Junction Adenocarcinoma;   Advanc...
Source: - Category: Research Source Type: clinical trials
AbstractPurpose of ReviewInterleukin-10 (IL-10) is a cytokine with anti-inflammatory properties, which induces activation and proliferation of antigen-activated intratumoral CD8+ T cells. This review discusses the evolution of pegylated IL-10 (pegilodecakin) from preclinical investigation through first-in-human studies in oncology.Recent FindingsPegilodecakin was evaluated across multiple advanced solid tumors in a large phase 1/1b trial alone and in combination with chemotherapy or anti-PD-1 antibodies. Pegilodecakin monotherapy had immunologic and clinical activity in renal cell carcinoma (RCC) and uveal melanoma. In com...
Source: Current Oncology Reports - Category: Cancer & Oncology Source Type: research
Source: Journal of the American Academy of Dermatology - Category: Dermatology Authors: Source Type: research
AbstractPurpose of the ReviewWe clarify clinical characteristics of patients with immune checkpoint inhibitor (ICI)-induced myositis.Recent FindingsIn 13 of 15 cases with ICI-induced myositis, the type of malignancy was melanoma. Eight, 4, and 3 patients received anti-PD-1 alone, anti-CTLA4 alone, and a combination of those, respectively. The mean period to the onset of ICI-induced myositis from the initiation of ICI was 4  weeks. Myocarditis was a complication in five patients. Seven of the patients died. The causes of death were myocarditis in three patients, respiratory muscle paralysis in two patients, and cancer ...
Source: Current Rheumatology Reports - Category: Rheumatology Source Type: research
ConclusionOur report demonstrates a rare endocrinopathy as a complication of combined PD-1 and CTLA-4 blockade. In addition, it provides evidence from the course of the disease that inflammation within the parathyroid gland is involved in the mechanism.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
uml;sl Replacements of animal models by advanced in vitro systems in biomedical research, despite exceptions, are currently still not satisfactory in reproducing the whole complexity of pathophysiological mechanisms that finally lead to disease. Therefore, preclinical models are additionally required to reflect analogous in vivo situations as found in humans. Despite proven limitations of both approaches, only a combined experimental arrangement guarantees generalizability of results and their transfer to the clinics. Although the laboratory mouse still stands as a paradigm for many scientific discoveries and breakthro...
Source: Viruses - Category: Virology Authors: Tags: Review Source Type: research
ConclusionMAGE-A and PD-L1 expression is increased in advanced disease and associated with shorter PFS. Furthermore, MAGE-A expression was significantly associated with higher-grade and -stage disease and associated with shorter RFS and PFS. The worse prognosis associated with MAGE-A+/PD-L1+  provides evidence that a combinatorial treatment strategy co-targeting MAGE/PD-L1 might be feasible. Further studies are needed to validate these findings.
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
CCR Grand Rounds F. Stephen Hodi, M.D., is the Director of the Melanoma Center and the Center for Immuno-Oncology at Dana-Farber/Brigham and Women's Cancer Center and Professor of Medicine at Harvard Medical School. He received his MD degree from Cornell University Medical College in 1992. Dr. Hodi completed his postdoctoral training in Internal Medicine at the Hospital of the University of Pennsylvania and Medical Oncology training at Dana-Farber cancer Institute where he joined the faculty in 1995. His research focuses on gene therapy, the development of immune therapies, and first-in-human studies for malignant melanoma...
Source: Videocast - All Events - Category: General Medicine Tags: Upcoming Events Source Type: video
Hematopoietic stem cell transplantation (HCT), which is increasingly used to treat patients with malignant and non-malignant conditions, is associated with increased risk for malignancies, including skin cancers. Data on incidence is incomplete, however, as more recent practices have utilized different donor sources and reduced-intensity conditioning regimens. In a contemporary cohort of 1,974 allogeneic HCT  patients, Wu and colleagues found significantly increased incidences of basal cell carcinoma, squamous cell carcinoma, and melanoma.
Source: Journal of Investigative Dermatology - Category: Dermatology Tags: Clinical Snippets Source Type: research
(University of Texas M. D. Anderson Cancer Center) Melanoma tumors that have spread to the brain are equipped to thwart immunotherapies and targeted therapies that succeed against tumors growing in other sites. Researchers at the University of Texas MD Anderson Cancer Center report in Cancer Discovery that the heavy reliance of these tumors on a specific metabolic pathway presents a potentially new therapeutic against these lethal tumors.
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news
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