CURE OM Forum


Welcome to the CURE OM Forum, a community bulletin board designed to address the needs of the ocular melanoma community – patients and caregivers alike. Here you’ll find answers to questions about OM diagnosis and treatment, and support from people from all stages, levels of treatment and from all over the world.

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My husband has developed a sunburn like rash on his face from selumetinib.  Anyone have that and what can be done?  Thanks, Margaret

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My husband has developed a sunburn like rash on his face from selumetinib.  Anyone have that and what can be done?  Thanks, Margaret

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Julieanne's picture
Replies 13
Last reply 8/11/2012 - 10:08pm

If my primary physician is not at all familiar with OM (choroidal melanoma) and his suggested treatment following initial diagnosis and subsequent plaque treatment consists of blood testing only, what could I do to obtain a list of options regarding experts for follow-up treatment?

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ThatHomeschoolDad's picture
Replies 1
Last reply 7/25/2012 - 7:24am
Replies by: RobC

Not for nothing, but if, as indicated at the Jeff conference, you want this to be a vibrant board and a realistic alternative to the Ocu-Mel list, you'll have to police spam.  You might also consider a new backend architecture that dramatically reduces the lag time after each submit.

--Tom

Keep Rowing!

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Hey all,

 

Just read article where anti-pd-1 drugs work best in tumors with protein pd-L1?  Anyone know if ocular melanoma has this protein?  We were tested for gnaq/gna11 and do have gnaq mutation.  All help is welcomed.  We are starting mek trial with selumetinib next week.  Will let you know how that goes.  Margaret

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Hey all,

 

Just read article where anti-pd-1 drugs work best in tumors with protein pd-L1?  Anyone know if ocular melanoma has this protein?  We were tested for gnaq/gna11 and do have gnaq mutation.  All help is welcomed.  We are starting mek trial with selumetinib next week.  Will let you know how that goes.  Margaret

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eyecancerny's picture
Replies 6
Last reply 7/13/2012 - 4:46pm

Todays NY Times featured an article on the genetic testing for OM featuring Dr. Harbour.  Here's the link:

http://www.nytimes.com/2012/07/10/health/genetic-test-changes-game-in-cancer-prognosis.html?_r=1&pagewanted=all

For those of us that attended the CURE OM conference there's nothing new here, but for others there's some valuable information.  

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We are still looking for an anti-pd-1 trial in nashville, atlanta, or close to chattanooga, tn.  Anybody know any that are in the works for 2012 or early 2013?  It looks like that bms would initiate more trials for ocular melanoma people who have progressed on yervoy as it seems the viable next step.  Please help us if you know of any.  thanks, Margaret Rogers

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We are still looking for an anti-pd-1 trial in nashville, atlanta, or close to chattanooga, tn.  Anybody know any that are in the works for 2012 or early 2013?  It looks like that bms would initiate more trials for ocular melanoma people who have progressed on yervoy as it seems the viable next step.  Please help us if you know of any.  thanks, Margaret Rogers

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It looks like substantially inhibiting the (re)activation of the stem cells of cancers is now possible by inhibiting the NOTCH pathways.

 

It was just done with leukemia in animals using a monoclonal antibody. The leukemia initiating cells did not survive. They were able, not only to get rid of cancerous cells, but also of the dormant stem cells starting it all.

 

I quote from the news release at UC San Diego:

Date: July 02, 2012 

Researchers Block Pathway to Cancer Cell Replication

NOTCH1 Signaling Promotes T-Cell Acute Lymphoblastic Leukemia-Initiating Cell Regeneration

Research suggests that patients with leukemia sometimes relapse because standard chemotherapy fails to kill the self-renewing leukemia initiating cells, often referred to as cancer stem cells.  In such cancers, the cells lie dormant for a time, only to later begin cloning, resulting in a return and metastasis of the disease.

One such type of cancer is called pediatric T cell acute lymphoblastic leukemia, or T-ALL, often found in children, who have few treatment options beyond chemotherapy.

A team of researchers – led by Catriona H. M. Jamieson, MD, PhD, associate professor of medicine at the University of California, San Diego School of Medicine and director of Stem Cell Research at UC San Diego Moores Cancer Center – studied these cells in mouse models that had been transplanted with human leukemia cells. They discovered that the leukemia initiating cells which clone, or replicate, themselves most robustly activate the NOTCH1 pathway, usually in the context of a mutation.

Earlier studies showed that as many as half of patients with T-ALL have mutations in the NOTCH1 pathway – an evolutionarily conserved developmental pathway used during differentiation of many cell and tissue types.  The new study shows that when NOTCH1 activation was inhibited in animal models using a monoclonal antibody, the leukemia initiating cells did not survive.  In addition, the antibody treatment significantly reduced a subset of these cancer stem cells (identified by the presence of specific markers, CD2 and CD7, on the cell surface).

“We were able to substantially reduce the potential of these cancer stem cells to self-renew,” said Jamieson.  “So we’re not just getting rid of cancerous cells: we’re getting to the root of their resistance to treatment – leukemic stem cells that lie dormant.”

The study results suggest that such therapy would also be effective in other types of cancer stem cells, such as those that cause breast cancer, that also rely on NOTCH1 for self-renewal. 

“Therapies based on monoclonal antibodies that inhibit NOTCH 1 are much more selective than using gamma-secretase inhibitors, which also block other essential cellular functions in addition to the NOTCH1 signaling pathway,” said contributor A. Thomas Look, MD of Dana-Farber/Children Hospital Cancer Center in Boston. “We are excited about the promise of  NOTCH1-specific antibodies to counter resistance to therapy in T-ALL and possibly additional types of cancer.”

In investigating the role of NOTCH1 activation in cancer cell cloning, the researchers showed that leukemia initiating cells possess enhanced survival and self-renewal potential in specific blood-cell, or hematopoietic, niches: the microenvironment of the body in which the cells live and self-renew.

The scientists studied the molecular characterization of CD34+ cells – a protein that shows expression in early hematopoietic cells and that facilitates cell migration – from a dozen T-ALL patient samples.

They found that mutations in NOTCH1 and other genes capable of promoting the survival of cancer stem cells co-existed in the CD34+ niche.  Mice transplanted with CD34-enriched NOTCH1 mutated T-ALL cells demonstrated significantly greater leukemic cloning potential than did mice without the NOTCH1 mutation.  The mutated cells were uniquely susceptible to targeted inhibition with a human monoclonal antibody, according to the scientists.

Additional contributors to the study include Wenxue Ma, Daniel J. Goff, Ifat Geron, Anil Sadarangani, Christina A. M. Jamieson, Angela C. Court, Alice Y. Shih, Qingfei Jiang, Christina C. Wu, Kristen M. Smith, Leslie A. Crews, Ida Deichaite, Sheldon R. Morris and Dennis A. Carson, UC San Diego Department of Medicine and Stem Cell Program, UC San Diego Moores Cancer Center; Alejandro Gutierrez, Dana-Farber/Children Hospital Cancer Center in Boston; and Kang Li, Ping Wei and Neil W. Gibson, Oncology Research Unit, Pfizer Global Research and Development, La Jolla Laboratories, San Diego."

 

Of course anyone with OM woudl be asking themselves if the NOTCH signaling pathways are also inportant in the proliferation of uveal melanoma (our cancer) stem cells. The answer is: YES! That was shown in a published study in February at Johns Hopkins. See http://www.ncbi.nlm.nih.gov/pubmed/22228632

 

It looks like our researchers are zooming in closer and closer to deal with the real culprits of many cancers. The specific cancer stem cells are the factories that need to be shut down.

 

Can't wait for the trials starting on the NOTCH inhibitors. Hopefully our doctors will catch on with this and start NOTCH inhibitor trials with uveal melanoma patients.

 

Maybe you guys could start asking questions about this with your doctors to make it visible for them? Can't hurt asking.

 

Peter L in NH

 

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Shelby - MRF's picture
Replies 1
Last reply 6/26/2012 - 5:29pm
Replies by: ThatHomeschoolDad

Posted on behalf of edamaser:

Delayed Systemic Recurrence of Uveal Melanoma
Kolandjian, Nathalie A. BA; Wei, Caimiao PhD; Patel, Sapna P. MD; Richard, Jessica L. ANP; Dett, Tina FNP; Papadopoulos, Nicholas E. MD; Bedikian, Agop Y. MDAbstract

Context: Metastatic uveal melanoma recurrence after >=10 years is not well studied in the clinical literature. This study describes the clinical characteristics and natural history of patients with delayed tumor recurrence.

Objective: To describe the characteristics of patients with delayed systemic recurrence of uveal melanoma and the natural history of the disease after recurrence.

Evidence Acquisition: This is a chart review of patients treated between 1994 and 2008 at The University of Texas, MD Anderson Cancer Center for uveal melanoma whose disease recurred >=10 years after treatment of the primary tumor.

Results: Of 463 patients treated for metastatic uveal melanoma, 305 developed systemic recurrence within 5 years from the time of diagnosis of primary melanoma, 97 developed systemic recurrences between 5 and 10 years, whereas 61 patients developed metastasis after >=10 years. The interval between primary to first systemic metastasis was a significant independent predictor of survival time from first systemic metastasis. The median survival time for patients with delayed metastatic recurrence after >=10 years was significantly longer than for patients who had intermediate or early systemic recurrence. Levels of lactate dehydrogenase, serum alkaline phosphatase, serum albumin, age, M-stage, and performance status at time of recurrence, as well as sex were also independent predictors of survival time from systemic recurrence.

Conclusions: Longer time interval between primary and first systemic metastasis is significantly correlated with prolonged survival. Patients who survive >=10 years without tumor metastasis after treatment for primary uveal melanoma cannot be considered cured. Prognosis remains poor for patients with metastatic uveal melanoma.

(C) 2012 Lippincott Williams & Wilkins, Inc. 

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edamaser's picture
Replies 2
Last reply 7/3/2012 - 9:39am
Replies by: paperdetective, RobC

Combination Small Molecule MEK and PI3K Inhibition Enhances Uveal Melanoma Cell Death in a Mutant GNAQ and GNA11 Dependent Manner

  1. Jahan S. Khalili1,
  2. Xiaoxing Yu1,
  3. Ji Wang2,
  4. Brendan C. Hayes1,
  5. Michael A. Davies3,
  6. Gregory Lizee4,
  7. Bita Esmaeli5, and
  8. Scott E. Woodman6,*

+ Author Affiliations


  1. 1Melanoma Medical Oncology, MD Anderson Cancer Center

  2. 2Thoracic and Cardiovascular surgery, MD Anderson cancer Center

  3. 3Melanoma Medical Oncology and Systems Biology, M. D. Anderson Cancer Center

  4. 4Melanoma Medical Oncology, M.D. Anderson Cancer Center

  5. 5Head and Neck Surgery, Section of Ophthalmology, MD Anderson Cancer Center

  6. 6Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center
  1. *Corresponding Author:
    Scott E. Woodman, Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, South Campus Research Building, SCR 2.3022, 7455 Fannin St., Houston, TX, 77054, United States swoodman@mdanderson.org
Abstract

Purpose: Activating-Q209L/P mutations in GNAQ or GNA11 (GNAQ/11) are present in ∼80% of uveal melanomas (UM). Mutant GNAQ/11 are not currently therapeutically targetable. Inhibiting key downstream effectors of GNAQ/11 represents a rational therapeutic approach for UMs that harbor these mutations. The MEK/MAPK and PI3K/AKT pathways are activated in UM. In this study, we test the effect of the clinically relevant small molecule inhibitors GSK1120212 (MEK inhibitor) and GSK2126458 (pan class I PI3K inhibitor) on UM cells with different GNAQ/11 mutations. Experimental Design: We use the largest set of genetically annotated uveal melanoma cell lines to-date to perform in vitro cellular signaling, cell cycle regulation, growth and apoptosis analyses. RNA interference and small molecule MEK and/or PI3K inhibitor treatment were employed to determine the dependency of cells with different GNAQ/11 mutation backgrounds on MEK/MAPK and/or PI3K/AKT signaling. Proteomic network analysis was performed to unveil signaling alterations in response to MEK and/or PI3K inhibition. Results: GNAQ/11 mutation status was not a determinant of whether cells would undergo cell cycle arrest or growth inhibition to MEK and/or PI3K inhibition. A reverse correlation was observed between MAPK and AKT phosphorylation after MEK or PI3K inhibition, respectively. Neither MEK nor PI3K inhibition alone was sufficient to induce apoptosis in the majority of cell lines; however, the combination of MEK + PI3K inhibitor treatment caused marked apoptosis in a GNAQ/11 mutant-dependent manner. Conclusions: MEK + PI3K inhibition may be an effective combination therapy in uveal melanoma given the inherent reciprocal activation of these pathways in UM.

  • Received December 14, 2011.
  • Revision received May 30, 2012.
  • Accepted June 1, 2012.
  • Copyright © 2012, American Association for Cancer Research. 

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On Sunday, August 12th, lace up your sneakers and join the Melanoma Foundation of New England at the starting line for the 2012 New Balance Falmouth Road Race. You can help spread awareness and educate others in the fight against melanoma.

Runners have been raising funds and awareness for the Melanoma Foundation of New England since 2004. Running for Cover, the Foundation's running team, has been running Falmouth for the past four years. We aim to raise more than $15,000 this year! Runner will be required to raise a minimum of $1,000 to help us reach our goal.

If you, or someone you know, is interested in joining Running for Cover, please visit our website, apply online, or email jshea@mfne.org.

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When you have been recently diagnosed with ocular melanoma, I believe there is nothing more inspirational to help one deal with it than Steve Job's (Apple's new deceased CEO) 2005 Stanford commencement speech, just after he was diagnosed with pancreatic cancer.

The video is heer http://www.youtube.com/watch?v=UF8uR6Z6KLc

The text is here http://facingcancertogether.witf.org/end-of-life/steve-jobs-inspirationa...

And if you want more inspiring details on Steve Jobs, I recommend the approved biography by Walter Isaacson.

 

Peter L in NH

diagnosed jan 2012, biopsied class 1b cells feb 2012,  proton beamed feb 2012, currently no mets, central vision on tumor eye virtually gone, vision in other (lazy) eye also part compromised

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Looking for trials of anti-pd-1.  Does anyone know of any that accept ocular primary and previous yervoy?  Tried Moffitt, but looking for something closer to TN.  All help is welcome.  Thanks, Margaret

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