Advances in immunotherapy for melanoma.
Ontology highlight
ABSTRACT:
SUBMITTER: Redman JM
PROVIDER: S-EPMC4744430 | biostudies-literature | 2016 Feb
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Paolo A Ascierto obtained his MD from the University of Naples, Italy, where he earned board certification in oncology. He is currently Director at the Unit of Melanoma, Cancer Immunotherapy and Innovative Therapy Unit, National Tumor Institute 'Fondazione G. Pascale', Naples, Italy. Before his present position, he served consecutive positions there as a postdoctoral fellow and then as Vice Director of the Department of Clinical Immunology. His major research interests have included genetics and proteomics research of melanoma, apoptosis and cell death in human cancer and the assessment of molecular markers for tumor progression in melanoma, as well as the management of targeted therapies for melanoma, vaccination treatments and biochemical and immunological monitoring. He has served as a principal investigator in numerous clinical trials and has been widely published in peer-reviewed journals on topics related to his interests. Ascierto has been an invited speaker at more than 200 national and international meetings and is an active member of the Italian Society of Medical Oncology (AIOM), the American Society of Clinical Oncology (ASCO), the European Society of Medical Oncology (ESMO), the European Organisation for Research and Treatment of Cancer (EORTC) and the International Society for Biological Therapy of Cancer (iSBTc). He is also the Editor-in-Chief of the Combination Strategies section of the Journal of Translational Medicine and serves as a scientific reviewer for several journals. James Larkin is a consultant medical oncologist specializing in the treatment of patients with cancer of the kidney and cancers of the skin, including melanoma. Larkin obtained a first-class degree in Natural Sciences from Cambridge University and undertook clinical training at Oxford University, qualifying in 1996. He underwent general medical training in London and, in 2001, won a Medical Research Council Fellowship for a Clinician, carrying out laboratory research at the Institute of Cancer Research (ICR), which led to the awarding of his PhD. He completed specialist training at The Royal Marsden Hospital and was appointed as a consultant in 2008. His research interests include the individualization of patient treatment in renal cancer and melanoma and the combination of novel targeted therapies for the treatment these diseases. He is the UK Chief Investigator for a number of clinical trials in melanoma and kidney cancer and has been awarded research grants from bodies including Cancer Research UK, the Wellcome Trust and the European Framework Programme 7. He is a member of the National Cancer Research Institute (NCRI) Melanoma Clinical Studies Group and Chair of both the NCRI Renal Cancer Clinical Studies Group and The Royal Marsden/ICR Committee for Clinical Research.
| S-EPMC6094603 | biostudies-literature
Project description:Uveal melanoma (UM) is the most common primary intraocular cancer in adults. The incidence in Europe and the United States is 6-7 per million population per year. Although most primary UMs can be successfully treated and locally controlled by irradiation therapy or local tumor resection, up to 50% of UM patients develop metastases that usually involve the liver and are fatal within 1 year. To date, chemotherapy and targeted treatments only obtain minimal responses in patients with metastatic UM, which is still characterized by poor prognosis. No standard therapeutic approaches for its prevention or treatment have been established. The application of immunotherapy agents, such as immune checkpoint inhibitors that are effective in cutaneous melanoma, has shown limited effects in the treatment of ocular disease. This is due to UM's distinct genetics, natural history, and complex interaction with the immune system. Unlike cutaneous melanomas characterized mainly by BRAF or NRAS mutations, UMs are usually triggered by a mutation in GNAQ or GNA11. As a result, more effective immunotherapeutic approaches, such as cancer vaccines, adoptive cell transfer, and other new molecules are currently being studied. In this review, we examine novel immunotherapeutic strategies in clinical and preclinical studies and highlight the latest insight in immunotherapy and the development of tailored treatment of UM.
| S-EPMC10823941 | biostudies-literature
Project description:Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Compared to cutaneous melanoma (CM), which mainly harbors BRAF or NRAS mutations, UM predominantly harbors GNAQ or GNA11 mutations. Although primary UM can be controlled locally, approximately 50% of patients still develop metastases. To date, there have been no standard therapeutic strategies for the prevention or treatment of metastases. Unfortunately, chemotherapy and targeted therapies only induce minimal responses in patients with metastatic UM, with a median survival time of only 4-5 months after metastasis detection. Immunotherapy agents, such as immune checkpoint inhibitors, have achieved pioneering outcomes in CM but have shown limited effects in UM. Researchers have explored several feasible checkpoints to identify options for future therapies. Cancer vaccines have shown little in the way of therapeutic benefit in patients with UM, and there are few ongoing trials providing favorable evidence, but adoptive cell transfer-related therapies seem promising and deserve further investigation. More recently, the immune-mobilizing monoclonal T-cell receptor against the cancer molecule tebentafusp showed impressive antitumor effects. Meanwhile, oncolytic viruses and small molecule inhibitors have also gained ground. This review highlights recent progress in burgeoning treatments and provides innovative insights on feasible strategies for the treatment of UM.
| S-EPMC9264803 | biostudies-literature
Project description:Melanoma is the most aggressive and deadly type of skin cancer and is known for its poor prognosis as soon as metastasis occurs. Since 2011, new and effective therapies for metastatic melanoma have emerged, with US Food and Drug Administration approval of multiple targeted agents, such as V-Raf murine sarcoma viral oncogene homolog B1/mitogen-activated protein kinase kinase inhibitors and multiple immunotherapy agents, such as cytotoxic T lymphocyte-associated protein 4 and anti-programmed cell death protein 1/ligand 1 blockade. Based on insight into the respective advantages of the above two strategies, the present article provided a review of clinical trials of the application of targeted therapy and immunotherapy, as well as novel approaches of their combinations for the treatment of metastatic melanoma in recent years, with a focus on upcoming initiatives to improve the efficacy of these treatment approaches for metastatic melanoma.
| S-EPMC10407994 | biostudies-literature
Project description:In 2011, two therapies were approved for the treatment of metastatic melanoma: ipilimumab, an immunotherapeutic agent, and vemurafenib, a BRAF kinase inhibitor. These approvals were based on data from phase III trials, which showed that treatment with these agents produced substantial improvements in overall survival (OS). Ipilimumab has been investigated in two phase III trials: one as monotherapy in patients with pretreated metastatic melanoma at a dose of 3 mg/kg and the second in combination with dacarbazine (DTIC) chemotherapy in patients with previously untreated metastatic melanoma at a dose of 10 mg/kg. Among the pretreated patients, ipilimumab monotherapy significantly improved median OS (Hazard ratio (HR): 0.66, P = 0.003) from 6.4 months in gp100 vaccine controls to 10.1 months. The rates of OS in the ipilimumab-alone group and the gp100 group, respectively, were 45.6% and 25.3% at 12 months and 23.5% and 13.7% at 24 months. In the second trial, OS was significantly longer in previously untreated patients receiving ipilimumab plus DTIC than those receiving DTIC plus placebo (11.2 months versus 9.1 months; HR: 0.72, P < 0.001), with higher survival rates in the ipilimumab plus DTIC group at 1 year (47.3% versus 36.3%), 2 years (28.5% versus 17.9%) and 3 years (20.8% versus 12.2%). When using ipilimumab in the clinic, special consideration should be given to immune-related adverse events (irAEs) and assessment of response. Established guidelines can be used to manage the majority of irAEs effectively. Proposed modifications made to the existing response criteria mean that the clinician can accurately detect immune-related responses that would have been considered representative of progressive disease using conventional criteria. Further research is warranted to establish how immunotherapeutic agents can be combined with conventional agents, with each other or with molecularly targeted agents such as vemurafenib, to further optimise clinical outcomes.
| S-EPMC6278954 | biostudies-literature
Project description:Survival for patients with glioblastoma, the most common high-grade primary CNS tumor, remains poor despite multiple therapeutic interventions including intensifying cytotoxic therapy, targeting dysregulated cell signaling pathways, and blocking angiogenesis. Exciting, durable clinical benefits have recently been demonstrated for a number of other challenging cancers using a variety of immunotherapeutic approaches. Much modern research confirms that the CNS is immunoactive rather than immunoprivileged. Preliminary results of clinical studies demonstrate that varied vaccine strategies have achieved encouraging evidence of clinical benefit for glioblastoma patients, although multiple variables will likely require systematic investigation before optimal outcomes are realized. Initial preclinical studies have also revealed promising results with other immunotherapies including cell-based approaches and immune checkpoint blockade. Clinical studies to evaluate a wide array of immune therapies for malignant glioma patients are being rapidly developed. Important considerations going forward include optimizing response assessment and identifiying correlative biomarkers for predict therapeutic benefit. Finally, the potential of complementary combinatorial immunotherapeutic regimens is highly exciting and warrants expedited investigation.
| S-EPMC4201077 | biostudies-literature
Project description:Immunotherapy is a cornerstone in the treatment of melanoma, and is intended to modulate the host immunity against the tumor. Immunotherapy can be used in an adjuvant setting, after complete surgical excision in patients with a high risk of disease relapse and as a treatment in advanced (unresectable or metastatic) stages. Development of novel therapeutic approaches and the optimization of existing therapies hold a great promise in the field of melanoma therapy research. Different clinical trials are ongoing, and immunotherapy is showing the ability to confirm durable clinical benefits in selected groups of melanoma patients. The aim of this review is to summarize different types of immunotherapy agents, as well as to discuss different strategies, complementary regimens, and possible biomarkers of response to the treatment.
| S-EPMC4049781 | biostudies-literature
Project description:Harnessing the immune system to attack cancer cells has represented a holy grail for greater than 100years. While prospects of tumor-selective durable immune based therapies have provided small clinical signals for many decades, recent years have demonstrated a virtual explosion in progress. Melanoma has led the field of cancers in which immunotherapy has produced major clinical inroads. The most significant and impactful immunotherapies for melanoma utilize immune checkpoint inhibition to stimulate T cell mediated tumor killing. The major targets of checkpoint blockade have thus far been CTLA4 and PD1, two key receptors for central and peripheral immune tolerance. This review discusses current understanding of how these checkpoint blockade therapeutics have led to major clinical responses in patients with advanced melanoma. It is likely that we are poised to see significantly greater anti-cancer immunotherapy efficacy, both in improving response rates and durability for melanoma, and for other less immunogenic malignancies.
| S-EPMC5569887 | biostudies-other
Project description:The immunotherapy is currently changing the landscape of oncology. Nowadays the standard of care in metastatic or unresectable melanoma patients include immunomodulating modalities such as anti-PD-1 drugs (nivolumab, pembrolizumab) and anti-CTLA-4 antibody ipilimumab. The improvements of progression free survival and overall survival connected with those treatments were unprecedented and have been confirmed in stage III trials. The efficacy of immunotherapy in metastatic setting can be further upgraded in some groups of patients by combining both types of antibodies. Latest clinical data suggest that treatment with immunotherapy can be also favorable for patients in adjuvant setting. Other treatment approaches based on immunological response (e.g. oncolytic viruses or adoptive cell therapy) have been proven useful in specific clinical situations. The future of melanoma treatment is still evolving, new molecular targets are being invented and hopefully current endeavors will led to further improvement of patients' survival. This review aims to summarize current state of immunotherapy in melanoma and identifying possible directions of development.
| S-EPMC5885078 | biostudies-literature
Project description:To date, the skin remains the most common cancer site among Caucasians in the western world. The complex, layered structure of human skin harbors a heterogenous population of specialized cells. Each cell type residing in the skin potentially gives rise to a variety of cancers, including non-melanoma skin cancer, sarcoma, and cutaneous melanoma. Cutaneous melanoma is known to exacerbate and metastasize if not detected at an early stage, with mutant melanomas tending to acquire treatment resistance over time. The intricacy of melanoma thus necessitates diverse and patient-centered targeted treatment options. In addition to classical treatment through surgical intervention and radio- or chemotherapy, several systemic and intratumoral immunomodulators, pharmacological agents (e.g., targeted therapies), and oncolytic viruses are trialed or have been recently approved. Moreover, utilizing combinations of immune checkpoint blockade with targeted, oncolytic, or anti-angiogenic approaches for patients with advanced disease progression are promising approaches currently under pre-clinical and clinical investigation. In this review, we summarize the current 'state-of-the-art' as well as discuss emerging agents and regimens in cutaneous melanoma treatment.
| S-EPMC8123429 | biostudies-literature