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staying on zelboraf FOREVER

Forums Cutaneous Melanoma Community staying on zelboraf FOREVER

  • Post
    boot2aboot
    Participant

       

      For all of us Braf + people we might soon one day be able to treat our mel like a chronic condition:

       

      For all of us Braf + people we might soon one day be able to treat our mel like a chronic condition:

       

       

      Vemurafenib resistance is characterized by a diminished apoptosis (programmed cancer cell death) response. According to the researchers, the balance between apoptosis and cell survival is regulated by a family of proteins. The survival of melanoma cells is controlled, in part, by an anti-apoptotic protein (Mcl-1) that is regulated by a particular kind of inhibitor.

      Their current findings, tested in six different models of vemurafenib resistance and in both test tube studies and in melanoma patients, demonstrated an induced apoptosis response and tumor regression when the XL888 inhibitor restored the effectiveness of vemurafenib.

      The study appeared in a recent issue of Clinical Cancer Research, a publication of the American Association for Cancer Research.

      "The impressive clinical response of melanoma patients to vemurafenib has been limited by drug resistance, a considerable challenge for which no management strategies previously existed," said study co-author Keiran S. M. Smalley, Ph.D., of Moffitt's departments of Molecular Oncology and Cutaneous Oncology. "However, we have demonstrated for the first time that the heat shock protein-90 (HSP90) inhibitor XL888 overcomes resistance through a number of mechanisms."

      The diversity of resistance mechanism has been expected to complicate the design of future clinical trials to prevent or treat resistance to inhibitors such as vemurafenib.

      "That expectation led us to hypothesize that inhibitor resistance might best be managed through broadly targeted strategies that inhibit multiple pathways simultaneously," explained Smalley.

      The HSP90 family was known to maintain cancer cells by regulating cancer cells, making it a good target for treatment. According to the authors, the combination of vemurafenib and XL888 overcame vemurafenib resistance by targeting HSP90 through multiple signaling pathways.

      There was already evidence that HSP90 inhibitors could overcome multiple drug chemotherapy resistance mechanisms in a number of cancers, including non-small lung cancer and breast cancer. Because XL888 is a novel, orally available inhibitor of HSP90, the researchers hoped that it would arrest the cancer cell cycle in melanoma cell lines.

      In their study, the inhibition of HSP90 led to the degradation of the anti-apoptopiuc Mcl-1 protein. The responses to XL888 were characterized as "highly durable with no resistant colonies emerging following four weeks of continuous drug treatment." In other studies not using XL888, resistant colonies "emerged in every case," they reported.

      "We have shown for the first time that all of the signaling proteins implicated in vemurafenib resistance are 'clients' of HSP90 and that inhibition of HSP90 can restore sensitivity to vemurafenib," concluded Smalley and his colleagues. "Our study provides the rationale for the dual targeting of HSP90 with XL888 and vemurafenib in treating melanoma patients in order to limit or prevent chemotherapy resistance."

      Provided by H. Lee Moffitt Cancer Center & Research Institute

    Viewing 14 reply threads
    • Replies
        s Mom
        Participant

          What a hopeful study for those with the BRAF mutation!!  I will send the article to my son (who is BRAF +) and daughter-in-law (and the doctor, too).  I wonder if this combination therapy will go to a larger clinical trial for melanoma patients???  

          Thanks for the article…so hoping they are going to find a cure for this awful disease soon.

          Jeff's Mom

          s Mom
          Participant

            What a hopeful study for those with the BRAF mutation!!  I will send the article to my son (who is BRAF +) and daughter-in-law (and the doctor, too).  I wonder if this combination therapy will go to a larger clinical trial for melanoma patients???  

            Thanks for the article…so hoping they are going to find a cure for this awful disease soon.

            Jeff's Mom

              boot2aboot
              Participant

                on clinical trials.gov they pulled the XL888…went to Moffitt site as clinical trials site not updated enough…no sign…i will ask about this on March 30th…found my free airfare!

                heres hoping

                boots

                boot2aboot
                Participant

                  on clinical trials.gov they pulled the XL888…went to Moffitt site as clinical trials site not updated enough…no sign…i will ask about this on March 30th…found my free airfare!

                  heres hoping

                  boots

                  boot2aboot
                  Participant

                    on clinical trials.gov they pulled the XL888…went to Moffitt site as clinical trials site not updated enough…no sign…i will ask about this on March 30th…found my free airfare!

                    heres hoping

                    boots

                  s Mom
                  Participant

                    What a hopeful study for those with the BRAF mutation!!  I will send the article to my son (who is BRAF +) and daughter-in-law (and the doctor, too).  I wonder if this combination therapy will go to a larger clinical trial for melanoma patients???  

                    Thanks for the article…so hoping they are going to find a cure for this awful disease soon.

                    Jeff's Mom

                    benp
                    Participant

                      EGCG (Epigallocatechin-3-gallate) found in green tea is also a natural, potent HSP90 inhibitor (see, among many others, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2927993/?tool=pubmed).

                      Yet another reason to take EGCG!

                      benp
                      Participant

                        EGCG (Epigallocatechin-3-gallate) found in green tea is also a natural, potent HSP90 inhibitor (see, among many others, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2927993/?tool=pubmed).

                        Yet another reason to take EGCG!

                          boot2aboot
                          Participant

                            i have always drunk tons of green tea LOL…can you just buy this compound at vitamin shoppe?

                            boots

                            boot2aboot
                            Participant

                              i have always drunk tons of green tea LOL…can you just buy this compound at vitamin shoppe?

                              boots

                              FormerCaregiver
                              Participant

                                Boots, EGCG is readily available in the form of green tea tablets. However, I wonder how much one needs to take for it to be effective? I have read that green tea is an anticoagulant and may cause problems at high dosages.

                                Take care

                                Frank from Australia

                                FormerCaregiver
                                Participant

                                  Boots, EGCG is readily available in the form of green tea tablets. However, I wonder how much one needs to take for it to be effective? I have read that green tea is an anticoagulant and may cause problems at high dosages.

                                  Take care

                                  Frank from Australia

                                  FormerCaregiver
                                  Participant

                                    Boots, EGCG is readily available in the form of green tea tablets. However, I wonder how much one needs to take for it to be effective? I have read that green tea is an anticoagulant and may cause problems at high dosages.

                                    Take care

                                    Frank from Australia

                                    benp
                                    Participant

                                      Yeah you can actually. Apparently Now Foods makes a good one, but I'm sure plenty of others do too. 

                                      If you're going to drink green tea, best to drink matcha if available. Next best is sencha. 

                                      Tastes good too!

                                      benp
                                      Participant

                                        Yeah you can actually. Apparently Now Foods makes a good one, but I'm sure plenty of others do too. 

                                        If you're going to drink green tea, best to drink matcha if available. Next best is sencha. 

                                        Tastes good too!

                                        benp
                                        Participant

                                          Yeah you can actually. Apparently Now Foods makes a good one, but I'm sure plenty of others do too. 

                                          If you're going to drink green tea, best to drink matcha if available. Next best is sencha. 

                                          Tastes good too!

                                          boot2aboot
                                          Participant

                                            i have always drunk tons of green tea LOL…can you just buy this compound at vitamin shoppe?

                                            boots

                                          benp
                                          Participant

                                            EGCG (Epigallocatechin-3-gallate) found in green tea is also a natural, potent HSP90 inhibitor (see, among many others, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2927993/?tool=pubmed).

                                            Yet another reason to take EGCG!

                                            rbruce
                                            Participant

                                              Awesome news Boots, my Onc at UCSF has said from the beginning that he thinks we're getting closer to treating this as a chronic disease.  Now my hope is that we find the inhibitor for NRAS and C-KIT that works and add the HSP to that.  I go in tomorrow for scans, biopsy, etc for the PD-1 trial and should be starting on March 15 when I get back from a road trip.  Take care.  Robert

                                              rbruce
                                              Participant

                                                Awesome news Boots, my Onc at UCSF has said from the beginning that he thinks we're getting closer to treating this as a chronic disease.  Now my hope is that we find the inhibitor for NRAS and C-KIT that works and add the HSP to that.  I go in tomorrow for scans, biopsy, etc for the PD-1 trial and should be starting on March 15 when I get back from a road trip.  Take care.  Robert

                                                  boot2aboot
                                                  Participant

                                                    good luck with new therapy Robert! May it be 100% success! Praying for you anyhow.

                                                    Update on this post.

                                                    I corresponded with Dr Smalley and he said they should have this trial up and coming in the next 2-3 mos. at Moffitt.  It will be their front runner braf trial.

                                                    boots

                                                    boot2aboot
                                                    Participant

                                                      good luck with new therapy Robert! May it be 100% success! Praying for you anyhow.

                                                      Update on this post.

                                                      I corresponded with Dr Smalley and he said they should have this trial up and coming in the next 2-3 mos. at Moffitt.  It will be their front runner braf trial.

                                                      boots

                                                      boot2aboot
                                                      Participant

                                                        good luck with new therapy Robert! May it be 100% success! Praying for you anyhow.

                                                        Update on this post.

                                                        I corresponded with Dr Smalley and he said they should have this trial up and coming in the next 2-3 mos. at Moffitt.  It will be their front runner braf trial.

                                                        boots

                                                      rbruce
                                                      Participant

                                                        Awesome news Boots, my Onc at UCSF has said from the beginning that he thinks we're getting closer to treating this as a chronic disease.  Now my hope is that we find the inhibitor for NRAS and C-KIT that works and add the HSP to that.  I go in tomorrow for scans, biopsy, etc for the PD-1 trial and should be starting on March 15 when I get back from a road trip.  Take care.  Robert

                                                        washoegal
                                                        Participant

                                                          vemurafenib had such promise until the resistance problem started poping up.  If the answer to this can be found, at least for 50-60% of the population we're on the way to a cure!  Of course they we have to deal with the other skin cancers it causes (minor in comparison) and of course the COST.  But every day there is new hope for survivors/fighters.

                                                          Mary

                                                          Stage 3

                                                          washoegal
                                                          Participant

                                                            vemurafenib had such promise until the resistance problem started poping up.  If the answer to this can be found, at least for 50-60% of the population we're on the way to a cure!  Of course they we have to deal with the other skin cancers it causes (minor in comparison) and of course the COST.  But every day there is new hope for survivors/fighters.

                                                            Mary

                                                            Stage 3

                                                              Lisa13
                                                              Participant

                                                                Now they have to concentrate on the people who arn't BRAF positive (like me) and I know they're working on it.

                                                                Wishing you al the very best ๐Ÿ™‚

                                                                Lisa

                                                                Lisa13
                                                                Participant

                                                                  Now they have to concentrate on the people who arn't BRAF positive (like me) and I know they're working on it.

                                                                  Wishing you al the very best ๐Ÿ™‚

                                                                  Lisa

                                                                  Lisa13
                                                                  Participant

                                                                    Now they have to concentrate on the people who arn't BRAF positive (like me) and I know they're working on it.

                                                                    Wishing you al the very best ๐Ÿ™‚

                                                                    Lisa

                                                                  washoegal
                                                                  Participant

                                                                    vemurafenib had such promise until the resistance problem started poping up.  If the answer to this can be found, at least for 50-60% of the population we're on the way to a cure!  Of course they we have to deal with the other skin cancers it causes (minor in comparison) and of course the COST.  But every day there is new hope for survivors/fighters.

                                                                    Mary

                                                                    Stage 3

                                                                    Linny
                                                                    Participant

                                                                      This is very encouraging news! Thanks for posting this.

                                                                      May the day that melanoma is nothing more than a chronic condition arrive soon.

                                                                        deardad
                                                                        Participant

                                                                          I very excited to hear that they are on the way to finding a drug that will prevent resistance with Vemurafenib. My dad is now on his 7th month and will be scanned at the end of this month. Really hoping that it's still doing it's magic.

                                                                          Thanks for the post Boots.

                                                                          Nahmi (daughter)

                                                                          deardad
                                                                          Participant

                                                                            I very excited to hear that they are on the way to finding a drug that will prevent resistance with Vemurafenib. My dad is now on his 7th month and will be scanned at the end of this month. Really hoping that it's still doing it's magic.

                                                                            Thanks for the post Boots.

                                                                            Nahmi (daughter)

                                                                            deardad
                                                                            Participant

                                                                              I very excited to hear that they are on the way to finding a drug that will prevent resistance with Vemurafenib. My dad is now on his 7th month and will be scanned at the end of this month. Really hoping that it's still doing it's magic.

                                                                              Thanks for the post Boots.

                                                                              Nahmi (daughter)

                                                                            Linny
                                                                            Participant

                                                                              This is very encouraging news! Thanks for posting this.

                                                                              May the day that melanoma is nothing more than a chronic condition arrive soon.

                                                                              Linny
                                                                              Participant

                                                                                This is very encouraging news! Thanks for posting this.

                                                                                May the day that melanoma is nothing more than a chronic condition arrive soon.

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