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NRAS and BRAF Testiing

Forums General Melanoma Community NRAS and BRAF Testiing

  • Post
    ncdaniel
    Participant

      Since my the Melanoma in my wife has spread from her head ( Removed 2011 11.5 mm deep ) to her lungs in July 2012 meta sized to lung multiple spots with tumors a needle biopsy was done in 2012 of her lung tumor.The sample showed Melanoma (no surprise) but the sample was not big enough for Braf testing, The assumption was made that since her original tumor on her head was tested not to be  BRAF receptive so would her lung tumors. My question is should new samples be taken and tested?

      Since my the Melanoma in my wife has spread from her head ( Removed 2011 11.5 mm deep ) to her lungs in July 2012 meta sized to lung multiple spots with tumors a needle biopsy was done in 2012 of her lung tumor.The sample showed Melanoma (no surprise) but the sample was not big enough for Braf testing, The assumption was made that since her original tumor on her head was tested not to be  BRAF receptive so would her lung tumors. My question is should new samples be taken and tested? I have just read on this site about NRAS testing should this be done?  I am not sure I even understand NRAS but any thought would be appreciated. I know most of you are not medical people but living this makes you one pretty quick. Any advice would Help. My wife has had IL2 – not a responder, and had one dose of IPI /Yervoy and is now on high dose steroids 80mg now 60mg due to issue not sure when or if Yervoy will resume anybody with any experience with this?

      Daniel

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    • Replies
        kylez
        Participant
          Hi Daniel,

          On NRAS, so far I’ve only seen it used for about 5 clinical trials as an eligibility criteria, mostly MEK inhibitors. As far as I know from my oncologist it sonds like theyre stull trying to figure out how to target NRAS effectively. So other than trying to get into certain MEK trials I’m not sure how useful it would be, yet.

          C-KIT mutation testing would be something to ask about, present in about 10% cutaneous (skin-originating) melanomas.

          Some people who originally tester BRAF negative have been re-tested with a different newer test and come up positive, something else to look into.

          I dont know whether melanoma that was originally, truly, BRAF negative can later evolve a new mutation like BRAF — no idea.

          Several here have had severe immune reactions to IPI — NYMaren, Swannee, and a username beginning with Roxy are a few, whose situations resolved eventually with steroids.

          kylez
          Participant
            Hi Daniel,

            On NRAS, so far I’ve only seen it used for about 5 clinical trials as an eligibility criteria, mostly MEK inhibitors. As far as I know from my oncologist it sonds like theyre stull trying to figure out how to target NRAS effectively. So other than trying to get into certain MEK trials I’m not sure how useful it would be, yet.

            C-KIT mutation testing would be something to ask about, present in about 10% cutaneous (skin-originating) melanomas.

            Some people who originally tester BRAF negative have been re-tested with a different newer test and come up positive, something else to look into.

            I dont know whether melanoma that was originally, truly, BRAF negative can later evolve a new mutation like BRAF — no idea.

            Several here have had severe immune reactions to IPI — NYMaren, Swannee, and a username beginning with Roxy are a few, whose situations resolved eventually with steroids.

              kylez
              Participant
                Er, that’s NYKaren, Swanee and Roxy1453.
                kylez
                Participant
                  Er, that’s NYKaren, Swanee and Roxy1453.
                  kylez
                  Participant
                    Er, that’s NYKaren, Swanee and Roxy1453.
                  kylez
                  Participant
                    Hi Daniel,

                    On NRAS, so far I’ve only seen it used for about 5 clinical trials as an eligibility criteria, mostly MEK inhibitors. As far as I know from my oncologist it sonds like theyre stull trying to figure out how to target NRAS effectively. So other than trying to get into certain MEK trials I’m not sure how useful it would be, yet.

                    C-KIT mutation testing would be something to ask about, present in about 10% cutaneous (skin-originating) melanomas.

                    Some people who originally tester BRAF negative have been re-tested with a different newer test and come up positive, something else to look into.

                    I dont know whether melanoma that was originally, truly, BRAF negative can later evolve a new mutation like BRAF — no idea.

                    Several here have had severe immune reactions to IPI — NYMaren, Swannee, and a username beginning with Roxy are a few, whose situations resolved eventually with steroids.

                    Tim–MRF
                    Guest

                      Though tumors can continue to mutate and evolve, I don't believe melanoma mutates from being BRAF wild type to BRAF mutant.  Having said this, a lot of tests get it wrong so re-testing is not a bad idea.

                      About half of cutaneous melanomas have mutated BRAF, mostly in melanomas that show up with moderate UV/sun exposure and mostly associated with a lot of moles.  About 15% of cutaneous melanomas have mutated NRAS.  This is a step further up in the signaling pathway.  In other words, the cell has a number of signalling pathways that allow various messages to be transmited from the cell surface to the cell nucleus.  Each pathway has a series of steps, and one step signals the next step.  One such pathway includes NRAS, which signals BRAF, which signals MEK, which signals ERK.  In about half of melanomas, the BRAF step is turned to the "on" position even though the step before it, NRAS, is not turned on.  In about 15%, the NRAS step is stuck in the "on" position.  

                      Doctors now have drugs that block the function of BRAF, shutting that switch down.  They also have, in late state development, some MEK inhibitors that block the step after BRAF.  Studies suggest that combining a BRAF inhibitor and a MEK inhibitor gives better and longer responses with fewer side effects.

                      For NRAS mutations the challenges are greater.  One approach is to use MEK along, and that has had moderate success. Because NRAS is not easily targeted, researchers are looking for other approaches.  Another approach is to look beyond ERK to the next cascade involving a compound called CDK4.  At least one company has a small study combining a MEK inhibitor and a CDK4 inhibitor, and I believe that is open to NRAS mutations.

                      I know this sounds like alphabet soup, but the bottom line is this.  Melanomas should be tested for common mutations: BRAF, NRAS, and KIT.  This information will help inform the treatment approach.

                      Tim–MRF

                       

                       

                        Hstevens0072
                        Participant
                          I found out today I am negative for all three. Will this limit the number of trials I am eligible for?
                          Hstevens0072
                          Participant
                            I found out today I am negative for all three. Will this limit the number of trials I am eligible for?
                            Hstevens0072
                            Participant
                              I found out today I am negative for all three. Will this limit the number of trials I am eligible for?
                              kylez
                              Participant

                                I haven't seen any restriction for immunotherapies like anti-PD1, and the like. But the trials and drugs for targeted therapies, that mention mutations as entracnce criteria, yes. I can't get into any BRAF+ trials or drugs because I'm wild type for that, and CKIT as well.

                                kylez
                                Participant

                                  I haven't seen any restriction for immunotherapies like anti-PD1, and the like. But the trials and drugs for targeted therapies, that mention mutations as entracnce criteria, yes. I can't get into any BRAF+ trials or drugs because I'm wild type for that, and CKIT as well.

                                  kylez
                                  Participant

                                    I haven't seen any restriction for immunotherapies like anti-PD1, and the like. But the trials and drugs for targeted therapies, that mention mutations as entracnce criteria, yes. I can't get into any BRAF+ trials or drugs because I'm wild type for that, and CKIT as well.

                                    kylez
                                    Participant

                                      So this must be the combo MEK + CDK4 trial you're talking about, Tim: NCT01781572. And the Novartis web page for the LEE011 drug in the trial has a nice picture of all the pathways you're talking about. 

                                      kylez
                                      Participant

                                        So this must be the combo MEK + CDK4 trial you're talking about, Tim: NCT01781572. And the Novartis web page for the LEE011 drug in the trial has a nice picture of all the pathways you're talking about. 

                                        kylez
                                        Participant

                                          So this must be the combo MEK + CDK4 trial you're talking about, Tim: NCT01781572. And the Novartis web page for the LEE011 drug in the trial has a nice picture of all the pathways you're talking about. 

                                        Tim–MRF
                                        Guest

                                          Though tumors can continue to mutate and evolve, I don't believe melanoma mutates from being BRAF wild type to BRAF mutant.  Having said this, a lot of tests get it wrong so re-testing is not a bad idea.

                                          About half of cutaneous melanomas have mutated BRAF, mostly in melanomas that show up with moderate UV/sun exposure and mostly associated with a lot of moles.  About 15% of cutaneous melanomas have mutated NRAS.  This is a step further up in the signaling pathway.  In other words, the cell has a number of signalling pathways that allow various messages to be transmited from the cell surface to the cell nucleus.  Each pathway has a series of steps, and one step signals the next step.  One such pathway includes NRAS, which signals BRAF, which signals MEK, which signals ERK.  In about half of melanomas, the BRAF step is turned to the "on" position even though the step before it, NRAS, is not turned on.  In about 15%, the NRAS step is stuck in the "on" position.  

                                          Doctors now have drugs that block the function of BRAF, shutting that switch down.  They also have, in late state development, some MEK inhibitors that block the step after BRAF.  Studies suggest that combining a BRAF inhibitor and a MEK inhibitor gives better and longer responses with fewer side effects.

                                          For NRAS mutations the challenges are greater.  One approach is to use MEK along, and that has had moderate success. Because NRAS is not easily targeted, researchers are looking for other approaches.  Another approach is to look beyond ERK to the next cascade involving a compound called CDK4.  At least one company has a small study combining a MEK inhibitor and a CDK4 inhibitor, and I believe that is open to NRAS mutations.

                                          I know this sounds like alphabet soup, but the bottom line is this.  Melanomas should be tested for common mutations: BRAF, NRAS, and KIT.  This information will help inform the treatment approach.

                                          Tim–MRF

                                           

                                           

                                          Tim–MRF
                                          Guest

                                            Though tumors can continue to mutate and evolve, I don't believe melanoma mutates from being BRAF wild type to BRAF mutant.  Having said this, a lot of tests get it wrong so re-testing is not a bad idea.

                                            About half of cutaneous melanomas have mutated BRAF, mostly in melanomas that show up with moderate UV/sun exposure and mostly associated with a lot of moles.  About 15% of cutaneous melanomas have mutated NRAS.  This is a step further up in the signaling pathway.  In other words, the cell has a number of signalling pathways that allow various messages to be transmited from the cell surface to the cell nucleus.  Each pathway has a series of steps, and one step signals the next step.  One such pathway includes NRAS, which signals BRAF, which signals MEK, which signals ERK.  In about half of melanomas, the BRAF step is turned to the "on" position even though the step before it, NRAS, is not turned on.  In about 15%, the NRAS step is stuck in the "on" position.  

                                            Doctors now have drugs that block the function of BRAF, shutting that switch down.  They also have, in late state development, some MEK inhibitors that block the step after BRAF.  Studies suggest that combining a BRAF inhibitor and a MEK inhibitor gives better and longer responses with fewer side effects.

                                            For NRAS mutations the challenges are greater.  One approach is to use MEK along, and that has had moderate success. Because NRAS is not easily targeted, researchers are looking for other approaches.  Another approach is to look beyond ERK to the next cascade involving a compound called CDK4.  At least one company has a small study combining a MEK inhibitor and a CDK4 inhibitor, and I believe that is open to NRAS mutations.

                                            I know this sounds like alphabet soup, but the bottom line is this.  Melanomas should be tested for common mutations: BRAF, NRAS, and KIT.  This information will help inform the treatment approach.

                                            Tim–MRF

                                             

                                             

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