«This is one of our major goals,» Sondek said, «to figure out how to inhibit that always - active Gα protein
in uveal melanoma.»
The paper is titled, «Effects of Selumetinib vs. Chemotherapy on Progression - Free Survival
in Uveal Melanoma.»
Not exact matches
Scientists have long suspected a genetic association with
uveal melanoma because one of two gene mutations is present
in approximately 70 percent of all tumors.
In cases of
uveal melanoma metastasis, patients typically succumb within two to eight months after diagnosis.
Research teams focused on both cutaneous and
uveal melanoma are fast - tracking discoveries into the clinical setting, and bringing novel therapeutic options to patients
in the Philadelphia region,» said Karen Knudsen, Director of the Sidney Kimmel Cancer Center.
In experiments with mice, the UC San Diego - led team showed that verteporfin also suppresses the growth of
uveal melanoma tumors derived from human tumors.
Approximately 2,000 people
in the United States are diagnosed with
uveal melanoma each year.
Uveal melanoma does not respond to the drugs given to patients with melanoma on the skin; and,
in fact, there is no drug approved specifically for treatment of the disease.
Though
uveal melanoma is rare — there are only 2,500 cases diagnosed
in the United States each year — about half of patients will develop metastatic disease, and survival for patients with advanced disease has held steady at nine months to a year for decades.
In the trial, researchers randomized 98 patients with metastatic
uveal melanoma and administered selumetinib to 47, of which 81 percent had a Gnaq or Gna11 mutation.
«This is the first study to show that a systemic therapy provides significant clinical benefit
in a randomized fashion to advanced
uveal melanoma patients, who have very limited treatment options,» said Richard D. Carvajal, MD, a medical oncologist at Memorial Sloan - Kettering and lead author on the study.
«If we can confirm selumetinib's effectiveness
in treating advanced
uveal melanoma
in this follow - up trial, it will become the standard therapy for this disease, forming a foundation for new drug combinations that could maximize selumetinib's MEK - inhibitor effect,» he said.
Patients with
uveal melanoma receive surgery to remove the tumor — and
in some advanced cases, the entire eye — as well as radiation therapy or chemotherapy.
Uveal melanoma is a cancer of the iris, ciliary body, or choroid — structures
in the eye collectively known as the uvea.
One hundred and one patients with metastatic
uveal melanoma at 15 centers
in the United States and Canada were randomized to receive either selumetinib or standard chemotherapy.
Several years ago, researchers found that 80 percent of patients with
uveal melanoma had mutations to GNAQ or GNA11, genes that activate signals
in the mitogen - activated protein kinase (MAPK) pathway.
In one of the balancing acts of medicine, the anti-inflammatory action of the drug also increases the risk for other conditions, in this case, a rare form of eye cancer, uveal melanom
In one of the balancing acts of medicine, the anti-inflammatory action of the drug also increases the risk for other conditions,
in this case, a rare form of eye cancer, uveal melanom
in this case, a rare form of eye cancer,
uveal melanoma.
About 1,500 cases of
uveal melanoma occur
in the United States each year, usually among older adults.
Unlike other solid tumors, there has been limited progress
in understanding the contribution of genetic risk factors to the development of
uveal melanoma, researchers say, primarily due to the absence of comprehensive genetic data from patients as the large sample cohorts for this rare cancer type have not been available for research.
Researchers expect the data presented
in this study to fuel the formation of large national and international research consortiums to conduct comprehensive, systematic analysis of inherited (germline) genome data
in large cohorts of
uveal melanoma patients.
Now our strong data shows the presence of novel genetic risk factors associated with this disease
in a general population of
uveal melanoma patients,» says Kirchhoff.
Previous clinical data suggests
uveal melanoma is more common
in Caucasians and individuals with light eye coloration; however, the genetic mechanisms underlying this cancer's development were largely unknown.
A Phase I / II, Open - label, Multi-center Study of the Safety and Efficacy of IMCgp100 using the Intra-patient Escalation Dosing Regimen
in Patients with Advanced
Uveal Melanoma
Furthermore, this compound displayed promising properties by impairing CXCR4 function
in three mouse models: paw inflammation, Matrigel plug angiogenesis, and
uveal melanoma micrometastasis.
Current clinical trials include combination of intrahepatic embolization and a radiosensitizer
in patients with
uveal melanoma and liver - only metastases, a phase I trial that evaluates a combination therapy of BCG with ipilimumab
in Stage III / IV melanoma, and several landmark international trials including a phase II trial that evaluates combination immunotherapy with nivolumab & ipilimumab.
[48] Mutations
in GNAQ or GNA11 occur
in the majority of
uveal melanomas and drive oncogenesis via activation of the phospholipase C / protein kinase C (PKC), Rho / Rac, and Yes - associated protein pathways.
The appearance of the moles and the melanomas
in these families can be unusual and affected families are also at increased risk of other cancers such as mesothelioma and eye (
uveal) melanoma.
While an
in - house (MH Stern's team) developed technique (biPAP - PCR) showed exquisite sensitivity for
uveal melanoma mutations (Madic, Clin Cancer Res 2012), we developed other ctDNA techniques (ddPCR and NGS - based techniques).
The Department of Translational Research hosts 5 technological platforms (Genomics, Protein arrays, High - content screening, Experimental radiotherapy and Preclinical investigation), 4 labeled teams (resistance to therapy
in breast cancers, translational pediatrics, angiogenesis, and immunotherapy) and 3 emergent teams (Circulating biomarkers,
uveal melanoma, and new targets
in triple negative breast cancers).
Analysis of cancers
in the pedigree of the proband carrying the S98R variant and
in two other pedigrees carrying clear loss - of - function alleles showed the presence of BAP1 - associated cancers such as renal cell carcinoma, mesothelioma and meningioma, but not
uveal melanoma.
Uveal melanoma is a melanoma that occurs either
in the coloured part of the eye (the iris) or other tissues nearby.
Chaired by Prof. Dirk Schadendorf, talks covered topics which included: melanoma epidemiology
in the
in period since the start of the German National Skin Cancer screening programme (Dr Andreas Strang); an overview of melanoma therapies used
in stage IV melanoma; adjuvant therapies and prognosis
in stage III melanoma (Dr Lisa Zimmer); tumour heterogeneity, plasticity and resistance
in melanoma (Alexander Roesch); epigenomics of normal and abnormal cell differentiation (Bernard Horsthermeke); and, genetics and epigenetics of
uveal melanoma (Michael Zeschnigk).
Uveitis is an inflammation of the eye's
uveal tract and glaucoma is a buildup of pressure
in the eye damaging the optic nerve.
Possible disease include keratitis (inflammation of the covering over the cornea), episcleritis (nflammation of the episcleral tissue), uveitis inflammation of the
uveal tract) and glaucoma (damange to the optic nerve due to high blood pressure
in the eye).
Sarah Hummel - «Neuromuscular Junction Disease
in a 1 - year - old Mixed Breed Dog» Nicholas Milano - «Osteonecrosis of the Jaw
in a Cocker Spaniel» Kevin Mu - «Malignant
Uveal Melanoma
in a 12 year old Labrador Retriever» Carly Augustyn - «Tibial Plateau Leveling Osteotomy
in a 4 - year - old Domestic Shorthair Cat» Ashley Newman - Moderator
Another clinical sign that is often present
in affected dogs is iris cysts (also called «
uveal cysts»).