MPIP: Melanoma Patients Information Page

The MPIP is the oldest and largest community of people affected by melanoma hosted through the Melanoma Research Foundation. It is designed to provide support and information to caregivers, patients, family and friends. Once you have been touched by melanoma—either as a patient or as a family member or friend of a patient—you become part of a community. It is not a community anyone joins willingly. But if you must be part of this group, you will find no better place to find the tools you need in your journey with this cancer, and the friends who can make that journey more bearable.

The information on the bulletin board is open and accessible to everyone. To add a new topic or to post a reply, you must be a registered user. Please note that you will be able to post both topics and replies anonymously even though you are logged in. All posts must abide by MRF posting policies.

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hawaii marcus's picture
Replies 1
Last reply 7/19/2013 - 8:47am

I am a new MM patient, and have just completed my first 2 surgeries in March and April. I started radiation on a Tomotherapy - Hi Art machine, and have completed 30 treaments to my face. I have an odd sunburn and my nose lights up like Rudolph, but I am doing well.

I am ready to heal, and move on with my life. This round is over, and now I await a new PET scan in September to see if there is any spreading of disease.  

My thoughts and prayers go out to those who I am reading about and their family struggles with this disease on these boards.

Keep up the fight, and enjoy your time with loved ones!

 

Aloha,

Marcus

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Commentary

Journal of Investigative Dermatology (2013) 133, 1928–1929; doi:10.1038/jid.2013.136

A STATement on Vemurafenib-Resistant Melanoma

Edward J Hartsough1 and Andrew E Aplin1

1Department of Cancer Biology and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA

Correspondence: Edward J. Hartsough or Andrew E. Aplin, Department of Cancer Biology and Kimmel Cancer Center, Thomas Jefferson University, 233 South 10th Street, Philadelphia, Pennsylvania 19107, USA. E-mail: ejh004@Jefferson.edu or Andrew.Aplin@Jefferson.edu

Abstract

Despite recent advancements in the treatment of late-stage mutant BRAF V600E/K melanomas, a major hurdle continues to be acquired resistance to BRAF inhibitors such as vemurafenib. The mechanisms for resistance have proven to be heterogeneous, emphasizing the need to use broad therapeutic approaches. In this issue, the study “Stat3-targeted therapies overcome the acquired resistance to vemurafenib in melanomas” by Liu et al. proposes that signal transducer and activator of transcription 3 (STAT3)–paired box 3 (PAX3) signaling may be a mechanism that is used by melanomas to resist RAF inhibitors.

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Original Article

Subject Category: Melanocytes/Melanoma

Journal of Investigative Dermatology (2013) 133, 2041–2049; doi:10.1038/jid.2013.32; published online 28 February 2013

Stat3-Targeted Therapies Overcome the Acquired Resistance to Vemurafenib in Melanomas

Fang Liu1,2,5, Juxiang Cao1,5, Jinxiang Wu1, Kayleigh Sullivan1, James Shen1, Byungwoo Ryu1, Zhixiang Xu3, Wenyi Wei4 and Rutao Cui1

  1. 1Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts, USA
  2. 2Department of Dermatology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
  3. 3Division of Hematology/Oncology, Department of Medicine, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, USA
  4. 4Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA

Correspondence: Fang Liu, Department of Dermatology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100043, China. E-mail: roseliufang@hotmail.com; Rutao Cui, Department of Dermatology, Boston University School of Medicine, 609 Albany Street, Boston, Massachusetts 02478, USA. E-mail: rutaocui@bu.edu

5These authors contributed equally to this work.

Received 3 August 2012; Revised 19 December 2012; Accepted 1 January 2013
Accepted article preview online 23 January 2013; Advance online publication 28 February 2013

Abstract

Vemurafenib (PLX4032), a selective inhibitor of Braf, has been approved by the US Food and Drug Administration for the treatment of unresectable or metastatic melanoma in patients with BrafV600E mutations. Many patients treated with vemurafenib initially display dramatic improvement, with decreases in both risk of death and tumor progression. Acquired resistance, however, rapidly arises in previously sensitive cells. We attempted to overcome this resistance by targeting the signal transducer and activator of transcription 3 (STAT3)–paired box homeotic gene 3 (PAX3)-signaling pathway, which is upregulated, owing to fibroblast growth factor 2 (FGF2) secretion or increased kinase activity, with the BrafV600E mutation. We found that activation of Stat3 or overexpression of PAX3 induced resistance to vemurafenib in melanoma cells. In addition, PAX3 or Stat3 silencing inhibited the growth of melanoma cells with acquired resistance to vemurafenib. Furthermore, treatment with the Stat3 inhibitor, WP1066, resulted in growth inhibition in both vemurafenib-sensitive and -resistant melanoma cells. Significantly, vemurafenib stimulation induced FGF2 secretion from keratinocytes and fibroblasts, which might uncover, at least in part, the mechanisms underlying targeting Stat3–PAX3 signaling to overcome the acquired resistance to vemurafenib. Our results suggest that Stat3-targeted therapy is a new therapeutic strategy to overcome the acquired resistance to vemurafenib in the treatment of melanoma.

Abbreviations:

FGF, fibroblast growth factor; PAX3, paired box homeotic gene 3

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bonusfries's picture
Replies 3
Last reply 7/19/2013 - 8:28am
Replies by: Tina D, Brendan, Anonymous

New diagnosee here. I had a mole on my abdomen that had been there for as long as I could remember, which starting growing both horizontally and vertically. Got in with a good dermatologist, excision, biopsy and then THE phone call soon afterwards. 

 

The tumor is >4mm, encapsulated with no satellites found in the tissue they originally removed. I was sent to UPenn for treatment, and I had a wide excision and lymph node removal on Friday. Now I'm just waiting for that next phone call.... to me the not knowing, the waiting is the worst part of this. Once I know then we can deal with it. My mind is just stuck trying to overvalue the good news and downplay the tumor depth.

 

And yeah I know exactly how this happened to me. A fair skinned white kid spends his whole childhood outside in a pool with no sunscreen... just another reason I'd like to smack my younger self.

 

Thanks for letting me vent, and thanks for the info I've already read on here. Here's to me being a regular for many many years to come.

 

Cheers!

Just do it

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I had a biopsy in June that came back as In situ melanoma.  Had the out patient surgery end of June and was just barely able to get by without a skin graft.  When I went back at two weeks for a wound check the PA said there was a problem with the margins and honestly I just stopped listening at that point because I just couldn't deal with it.  Went back yesterday to get the stitches out and met with the plastic surgeon who explained that while the pathology report indicated that he had gotten all of the melanoma there were some 'abnormal cells' in several areas around the melanoma.  So, in three months, when the wound has competely healed, he will go back and take 4 biopsies in those areas.  

So, if it's not cancer but just 'abnormal' cells what then?  Because we just barely got away without a skin graft now cutting more out later could be problematic - the melanoma was on the back of my leg just above my ankle.

Thanks for any insight - and no I did not get a copy of the pathology report...

 

 

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Have not posted in a while, but had a good follow-up today with my melanoma specialist. I became 3C in Sep 2012 when the melanoma spread to a single nearby lymph node (~18 months after initial diagnosis). I chose to "watch and wait" and today had another all clear visit - my next follow-up is in 6 months and I am scheduled to have a CT scan, an MRI of the brain, and full bloodwork. No PET scans.

It is interesting to me how scan type and frequency seem to vary a lot. Some people seem to have some type of scan every 3 months or so. Clearly, my oncologist is not a huge believer in these scans for detecting recurrence.  

Kevin   

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buffcody's picture
Replies 9
Last reply 7/30/2013 - 3:12pm

I was catching up on my MPIP Bulletin Board reading this morning and read a couple of posts suggesting that posting encouraging news is as important for people reading out here as more difficult experiences.  I was diagnosed at Stage IV a year ago June.  Operations to remove mets on lung and left buttock, SRS for two brain tumors, one course of  Yervoy.  I've been NED since the buttock operation on May 1.  I had two grand mal seizures on May 11, originally diagnosed as the result of a new brain tumor, later corrected to be a side effect of  hematoma from one of the previously radiated brain tumors. In the hospital afterwards for three days.  

 

Yesterday, after another brain MRI last week, my oncologist recommended brain surgery to remove the growing but dead leision manfiesting the hematoma.  Though still on anti-swelling and anti seizure medications, the latter for the long term, I'm feeling fine and intend to compete next week in swimming at the National Senior Games in Cleveland, a biannual event, in the 70-74 age group.  I've been able to  keep up my training through this  entire year, though admittedly at a reduced level and some weeks and months at zero. 

Brain surgery will take place sometime after next week, of course, not sure yet when but soon.  My oncologist at the Univerwsity of Michigan believes that the Yervoy helped me, but, since the only objective measure I have is that there were no new mets except one in my buttock that showed up after the four infusions, I don't fit any of the objective criteria for success (reduction in tumor load or reduction in growth). But whatever the cause of my relatively easy journey, I am most grateful that I'm able to be fully functional, albeit with legal restriction from driving till 6 months after the seizure, and knowing that there are an abundance of new treatments being developed if I need them in the future.

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François's picture
Replies 2
Last reply 7/16/2013 - 10:09pm
Replies by: DeniseK, awillett1991

8 days ago I had a Pet Scan which confirmed the mets in my liver (about 10) and one limph node in my lower chest. It seems that Zel had stopped working exactly after six month. My onc is very disappointed because mets in my lungs have disappeared and he doesn't understand why it worked in my lungs and not in the liver? Next step is to start a 3 cycle from next Tuesday with dacarbazin until next pet scan in September. He said that plan B is to fight with the social security to have access to Ipi. I am completely devastated, specially coming from a ned stage 8 weeks ago. I can't believe it, but I have faith and I am optimistic with this next treatment.

François

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casagrayson's picture
Replies 2
Last reply 7/16/2013 - 11:55pm
Replies by: casagrayson, Janner

Short bio:  Husband has had two primaries, both Stage 1 (one with some mitotic activity).  He has had many more BCC and squamous, and this year alone has had 5 Mohs procedures.  The last surgeries were for nodular cancers which were (finally) diagnosed as recurrent BCC, even though he never had any cancer/surgeries in that area.  

Latest derm visit found another suspicious spot.  Biopsied, with the following pathology:

"The speciment is a shave biopsy of skin present as multiple H&E stained sections on one slide.  Cytologic atypia is present and manifests as large nuclei, pleomorphism, and abnormal chromatin patterns.  No atypical mitotic figures are identified.  Architectural disorder is present and manifests as lentiginous hyperplasia, horizontal growth pattern, individual melanocytic hyperplasia and abnormal formed junctional nests that focally demonstrate bridging adjacent rete ridges.  There is an incidental angioma.  The melanocytic process extends to the deep and one lateral surgical margins."

No stains were performed.

The doctor's scheduler called today, said the doctor wanted to do a WLE, and we have an appointment in two weeks.

 

Here's my question.  In a person who has already had two primary melanomas, and who has had other "unusual" pathologies (they were worried about Merkel cell carcinoma or spindle cell, and quite frankly, never did come up with an answer that satisfied me), should we be dealing with a melanoma specialist instead of just a dermatologist (albeit a pretty good one, I think)?  Is there any reason we should be acting more aggressively (i.e. SNB or scans of any sort)?  I feel as if he is a ticking time bomb, and I want to proceed with the greatest amount of caution without "borrowing trouble".

 

Susan

Strength and Courage,

Susan

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Anonymous's picture
Anonymous
Replies 10
Last reply 7/23/2013 - 11:51am

Swelling that can be felt on the surface......if that were a tumor, would it be painful?

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Anonymous's picture
Anonymous
Replies 1
Last reply 7/16/2013 - 4:35pm
Replies by: Anonymous

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AllyNTAus's picture
Replies 7
Last reply 7/18/2013 - 9:51pm

Today marks 1 week since I had a large chunk of my right atrium removed to get rid of a nasty cardiac met that had popped up quite quickly. The surgery went really well, all the tumour was removed, but I had to have a pacemaker inserted. I believe there might have been some evidence seen of other mets but I have not seen any reports or talked in detail with the surgeon about this. All I know is that he has bought me some time to keep on fighting, because his words to my husband were that if we had not got this met out, I would have been dead in a few weeks, that's how much it was starting to block the chamber.

I am still recovering in hospital, having been more troubled since by some terrible gastro issues, which are being investigated. I had an irritable bowel before I came into hospital, and I think being pumped full of all sorts of drugs on a basically empty stomach just made things 100 times worse. Anyway should get some answers on this tomorrow.

Next step is to see my melanoma oncologist on Monday, and hopefully get my first infusion of Ipi. Just praying that can be given ok and that it kicks in quick!

It's been great to get support from everyone here, especially cardiac met buddy Amy
Cheers
Ally

A bad day's fishing beats a good day's work everytime

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Anonymous's picture
Anonymous
Replies 7
Last reply 7/17/2013 - 1:51pm
Replies by: Anonymous, awillett1991, DeniseK, 5374brian, DonnaK

My mom has stage IV. Adrenal glands, lymph nodes, spleen, vaginal and brain. Initially, she was tested to see if she had the mutated Braf gene. We were told she did not, so was not a fit for zelboraf. She is almost finished with yervoy and recently started WBR. the Dr. Told us today that they did some more tests and found that one of her tests showed that she does have the braf. Her Dr.suggested that she take zelboraf along with everything else that she's doing.
Anyone experience taking yervoy, zelboraf and WBR together???

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Anonymous's picture
Replies 7
Last reply 10/12/2013 - 6:04am
Replies by: rock, Anonymous, DeniseK, ecc26, POW

Hello everyone,

This is my first post but I have been reading this bulletin board almost daily.  All of your stories and words of encourgaement have been getting me through this toughest time in my life, so thank you. 

My mom has stage IV melanoma.  She was diagnosed in April 2013.  The doctors told us that she had tumors in her lymph nodes, adrenal gland and spleen.  It took a long time for them to get results back that would show whether or not she had the mutated BRAF gene (turns out that she didn't), so there was a long gap between her being diagnosed to her starting any kind of treatment.  While she was waiting, she started spotting.  She's 60 years old so it was unusual.  She went to her gyno and was told that she also had vaginal cancer (melanoma that spread).  Her gyno said that it was very possible to have missed this in a CT scan.  Doesn't this seem odd that world renowned Dr.'s and hospitals would miss this?? 

So, we received this news and still hopeful, she started her yervoy infusions.  She has not had many side effects to the Yervoy except fatigue.  She seemed well until recently.  About 3 weeks ago, she started acting "off" (calling people the wrong names and just more confused-highly unlike her).  Turns out, she had a small brain tumor that would be easy to remove.  The surgeon took it out and claimed that he got the whole thing.  Next, it was time to decide between Gamma Knife and Cyber Knife.  Her consultation was about 2 weeks after her surgery.  She went in for the consultation and they did an MRI to find that there is another tumor that is twice the size of the 1st one. 

I'm trying to stay positive but my family feels certain that this is a sign that things are on the decline and that her cancer is highly aggresive.  She has started whole brain radiation last Thursday (5 days per week for 3 weeks) and had another on Friday.  Friday night and all day Saturday, she was in tremendous pain.  She was holding her side, vomiting and complaining of sharp pain in her ab and back.  I fear that this a result of her adrenal gland tumor.  On Sunday, the pain subsided a bit and today she's status quo.  When the pain increases and you feel it a lot more than usual, does this typically mean that the tumor has grown???

The Dr. is telling us that there's no point in doing a CT scan until 3 weeks after her last Yervoy treatment but I fear that she's dying before me.  Not knowing is the hardest part for us.  If anyone has endured a similar experience and is willing to share, I would greatly appreciate it. 

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Tina D's picture
Replies 16
Last reply 7/18/2013 - 7:50pm

Lisa, Been thinking abt you and wondering how the appt went in Nashville? I am hoping you have good news abt the trials there for him.

Tina

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