I'm 74. oddly i don't really get fatigued. and i did not try lipoic acid since everything seems to be working well enough to control neuropathy and get my counts high enough for my next blood test. Will look it up, however.
my 6(8) hour infusions were cisplatin, taxol and herceptin - how just herceptin (keytruda).
yeah, but hair is just hair - would rather be living and bald. just wait until you lose your nose hairs (drip, drip) and the stuff in the nether region (feels very weird).
the thing that was bothering me and keeping me from sleeping was the steroids that they put me on (5 the night before chemo, 1 in the a.m. and p.m. for 4 days after) - plus my face got really red even with the allegra they told me to take. I am sleeping a lot these days but never that bad plus i try to walk 1-2 miles/day.
oh, i guess i'm dmmr, not pmmr which may make a difference. actually i wanted to get Jemperli (which is for pMMR) but since they said this was working, it WOULD be off label.
maybe you really need a second opinion!! (I thought about finding a gravesite but too depressing! instead, i'm booking foreign travel until i can't do it anymore. my oncologist hates it but i'm scheduling everything around chemo treatments. I do notice that i don't have much bladder control for about 4-5 days after chemo. need to wear a diaper on flights > 4 hours (which means i need to get manually patted down at the airport but whatever).
Thank you for sharing your journey and the helpful links. Love the foreign travel. Up yours, cancer! You go girl. Carpe Diem!
If you are dmmr have you seen the big news article from Sloan Kettering that was in the New England Journal of Medicine? It was on regular news outlets, too. The problem with the mismatch repair allowed the drug to target and strip cancer cells of protection and be DESTROYED. Here's the article . Dostarlimab is the drug they used.
The New England Journal of Medicine published a paper on April 27, 2025, that presents exciting new results from a clinical trial led by Memorial Sloan Kettering Cancer Center (MSK) gastrointestinal oncologists Andrea Cercek, MD, and Luis Diaz Jr., MD, that demonstrates how immunotherapy alone can help patients with MMRd cancers avoid surgery and preserve their quality of life. The results, presented simultaneously at the 2025 American Association of Cancer Research (AACR) Annual Meeting, showed that 80% of patients with several types of cancer treated with immunotherapy did not require surgery, radiation, or chemotherapy after six months of treatment with immunotherapy alone. Swim Across America awarded grants for the early-stage research and continues to award grants for the ongoing clinical trial.
Andrea Cercek, M.D., gastrointestinal oncologist and co-director of the Center for Young Onset Colorectal and Gastrointestinal Cancer at Memorial Sloan Kettering Cancer Center
Mismatch repair deficiency (MMRd) in cancer refers to a situation where tumor cells have defective mismatch repair (MMR) proteins, essential for correcting DNA errors during cell replication. This deficiency leads to the accumulation of mutations, including microsatellite instability (MSI), making tumors more prone to be recognized by the immune system. MMRd status is a significant factor in cancer treatment, particularly for immunotherapy, as it can predict response to immune checkpoint inhibitors.
The standard of care for many cancers that have this specific MMRd genetic mutation has been surgery, radiation, and chemotherapy. Still, the patients who responded positively to this clinical trial did not require surgery to remove an organ and did not experience chemotherapy or radiation, which improved their quality of life. This trial is the first time that immunotherapy has been shown to replace surgery for a variety of solid tumors.
“This study shows that immunotherapy can replace surgery, radiation and chemotherapy for mismatch repair-deficient solid tumors, which could help patients preserve their organs and avoid the harsh side effects of chemo and radiation,” said Andrea Cercek, M.D., gastrointestinal oncologist and co-director of the Center for Young Onset Colorectal and Gastrointestinal Cancer at Memorial Sloan Kettering Cancer Center. “Preserving a patient’s quality of life, while also successfully achieving positive results in eliminating their cancer, is the best possible outcome. They can return to their daily routines and maintain their independence.”
Luis Diaz, M.D., gastrointestinal oncologist and Head of the Division of Solid Tumor Oncology at Memorial Sloan Kettering Cancer Center
This phase 2 trial is an extension of a groundbreaking study, also funded in part by Swim Across America, in which all rectal cancer patients treated with the immunotherapy dostarlimab experienced a complete clinical response, meaning their tumors disappeared. This was the first time ever that a clinical trial had a 100% positive response rate.
Definitely save those hair accessories!
My hair grew back in a mop and I had it shaped up into a short style about 5 months after my last chemo. For whatever it’s worth, I kept it short and ditched the hair dryer & straightener. Very freeing and a time saver as well.
i was put in touch after the pathology diagnosis with a Palliative Care doctor. i only talked with him twice (trying to figure out whether or not to do chemo because i was VERY freaked) but he's connected me with a social worker and some other people (i may have to move into assisted living or ??? since i have no family).
Thank you for sharing your journey and the helpful links. Love the foreign travel. Up yours, cancer! You go girl. Carpe Diem!
If you are dmmr have you seen the big news article from Sloan Kettering that was in the New England Journal of Medicine? It was on regular news outlets, too. The problem with the mismatch repair allowed the drug to target and strip cancer cells of protection and be DESTROYED. Here's the article . Dostarlimab is the drug they used.
The New England Journal of Medicine published a paper on April 27, 2025, that presents exciting new results from a clinical trial led by Memorial Sloan Kettering Cancer Center (MSK) gastrointestinal oncologists Andrea Cercek, MD, and Luis Diaz Jr., MD, that demonstrates how immunotherapy alone can help patients with MMRd cancers avoid surgery and preserve their quality of life. The results, presented simultaneously at the 2025 American Association of Cancer Research (AACR) Annual Meeting, showed that 80% of patients with several types of cancer treated with immunotherapy did not require surgery, radiation, or chemotherapy after six months of treatment with immunotherapy alone. Swim Across America awarded grants for the early-stage research and continues to award grants for the ongoing clinical trial.
Andrea Cercek, M.D., gastrointestinal oncologist and co-director of the Center for Young Onset Colorectal and Gastrointestinal Cancer at Memorial Sloan Kettering Cancer Center
Mismatch repair deficiency (MMRd) in cancer refers to a situation where tumor cells have defective mismatch repair (MMR) proteins, essential for correcting DNA errors during cell replication. This deficiency leads to the accumulation of mutations, including microsatellite instability (MSI), making tumors more prone to be recognized by the immune system. MMRd status is a significant factor in cancer treatment, particularly for immunotherapy, as it can predict response to immune checkpoint inhibitors.
The standard of care for many cancers that have this specific MMRd genetic mutation has been surgery, radiation, and chemotherapy. Still, the patients who responded positively to this clinical trial did not require surgery to remove an organ and did not experience chemotherapy or radiation, which improved their quality of life. This trial is the first time that immunotherapy has been shown to replace surgery for a variety of solid tumors.
“This study shows that immunotherapy can replace surgery, radiation and chemotherapy for mismatch repair-deficient solid tumors, which could help patients preserve their organs and avoid the harsh side effects of chemo and radiation,” said Andrea Cercek, M.D., gastrointestinal oncologist and co-director of the Center for Young Onset Colorectal and Gastrointestinal Cancer at Memorial Sloan Kettering Cancer Center. “Preserving a patient’s quality of life, while also successfully achieving positive results in eliminating their cancer, is the best possible outcome. They can return to their daily routines and maintain their independence.”
Luis Diaz, M.D., gastrointestinal oncologist and Head of the Division of Solid Tumor Oncology at Memorial Sloan Kettering Cancer Center
This phase 2 trial is an extension of a groundbreaking study, also funded in part by Swim Across America, in which all rectal cancer patients treated with the immunotherapy dostarlimab experienced a complete clinical response, meaning their tumors disappeared. This was the first time ever that a clinical trial had a 100% positive response rate.
This is great news for many women with aggressive cancers. Sadly, my biomarker report card says that I’m proficient, but maybe there will soon be something equally hopeful for me and my sisters soon.
Are you on Herceptin/trastuzumab or Keytruda/pembrolizumab (or both)? These are different antibodies against different things.
Herceptin is against HER2, and Keytruda is against the immune inhibitor PD-1. Jemperli/dostarlimab is a different company's antibody against PD-1, and would be expected to have about the same effects as Keytruda. Jemperli is approved for dMMR endometrial cancers.
Thank you so very much for the clarification. I want to get on Herceptin/trastuzumab because my HER 2 score is 3+ , the worst. Insurance wouldn't approve it and won't until other treatments have proved useless. Right now I have "mixed results." My oncologist tried hard to get it for me, and also appealed to the drug company for compassionate freebie, but no luck. The justification for denial is that it isn't yet approved for uterine cancer - just breast cancer. I have Untited Health Medicare. Would love to hear from others if you got approved for Herceptin/trastuzumab with your insurance, and what insurance you have. Maybe I could use that to make an appeal. "All these other companies approve it, so join the club." I haven't seen PD-1 on my lab report. I'll look again. There is a study on using Ivermectin against PD one at Cedar Sinai in LA . Not sure how it worked out. Any know anything about Ivermectin use? It doesn't cost much so there isn't any incentive for drug companies to spend a lot of dollars to study it. No return on investment. If I'm pMMR how does that connect with PD -1, if at all?
Thank you so very much for the clarification. I want to get on Herceptin/trastuzumab because my HER 2 score is 3+ , the worst. Insurance wouldn't approve it and won't until other treatments have proved useless. Right now I have "mixed results." My oncologist tried hard to get it for me, and also appealed to the drug company for compassionate freebie, but no luck. The justification for denial is that it isn't yet approved for uterine cancer - just breast cancer. I have Untited Health Medicare. Would love to hear from others if you got approved for Herceptin/trastuzumab with your insurance, and what insurance you have. Maybe I could use that to make an appeal. "All these other companies approve it, so join the club." I haven't seen PD-1 on my lab report. I'll look again. There is a study on using Ivermectin against PD one at Cedar Sinai in LA . Not sure how it worked out. Any know anything about Ivermectin use? It doesn't cost much so there isn't any incentive for drug companies to spend a lot of dollars to study it. No return on investment. If I'm pMMR how does that connect with PD -1, if at all?
ive got basic medicare w aarp medigap g. love it. basically if medicare approves it, medigap pays the copay. basic medicare has no maximum out of pocket which is VERY bad but the additional medigap does. have to get your own drug policy tho
You should be eligible to take Enhertu. This is an antibody-drug conjugate that targets cancers that express HER2. It is approved for all solid tumors that are 3+ for HER2. I expect your oncologist will recommend this tomorrow.
People on this forum who have taken it have found it to work (at least for a while) and for it to be quite tolerable.
Thank you! My doc said something about a cousin drug to Traszumabab that I could take if the chemo I'm on doesn't work. I bet this is it. Wish I didn't have to wait. I'll ask her about Enhertu.
Thank you for sharing your journey and the helpful links. Love the foreign travel. Up yours, cancer! You go girl. Carpe Diem!
If you are dmmr have you seen the big news article from Sloan Kettering that was in the New England Journal of Medicine? It was on regular news outlets, too. The problem with the mismatch repair allowed the drug to target and strip cancer cells of protection and be DESTROYED. Here's the article . Dostarlimab is the drug they used.
The New England Journal of Medicine published a paper on April 27, 2025, that presents exciting new results from a clinical trial led by Memorial Sloan Kettering Cancer Center (MSK) gastrointestinal oncologists Andrea Cercek, MD, and Luis Diaz Jr., MD, that demonstrates how immunotherapy alone can help patients with MMRd cancers avoid surgery and preserve their quality of life. The results, presented simultaneously at the 2025 American Association of Cancer Research (AACR) Annual Meeting, showed that 80% of patients with several types of cancer treated with immunotherapy did not require surgery, radiation, or chemotherapy after six months of treatment with immunotherapy alone. Swim Across America awarded grants for the early-stage research and continues to award grants for the ongoing clinical trial.
Andrea Cercek, M.D., gastrointestinal oncologist and co-director of the Center for Young Onset Colorectal and Gastrointestinal Cancer at Memorial Sloan Kettering Cancer Center
Mismatch repair deficiency (MMRd) in cancer refers to a situation where tumor cells have defective mismatch repair (MMR) proteins, essential for correcting DNA errors during cell replication. This deficiency leads to the accumulation of mutations, including microsatellite instability (MSI), making tumors more prone to be recognized by the immune system. MMRd status is a significant factor in cancer treatment, particularly for immunotherapy, as it can predict response to immune checkpoint inhibitors.
The standard of care for many cancers that have this specific MMRd genetic mutation has been surgery, radiation, and chemotherapy. Still, the patients who responded positively to this clinical trial did not require surgery to remove an organ and did not experience chemotherapy or radiation, which improved their quality of life. This trial is the first time that immunotherapy has been shown to replace surgery for a variety of solid tumors.
“This study shows that immunotherapy can replace surgery, radiation and chemotherapy for mismatch repair-deficient solid tumors, which could help patients preserve their organs and avoid the harsh side effects of chemo and radiation,” said Andrea Cercek, M.D., gastrointestinal oncologist and co-director of the Center for Young Onset Colorectal and Gastrointestinal Cancer at Memorial Sloan Kettering Cancer Center. “Preserving a patient’s quality of life, while also successfully achieving positive results in eliminating their cancer, is the best possible outcome. They can return to their daily routines and maintain their independence.”
Luis Diaz, M.D., gastrointestinal oncologist and Head of the Division of Solid Tumor Oncology at Memorial Sloan Kettering Cancer Center
This phase 2 trial is an extension of a groundbreaking study, also funded in part by Swim Across America, in which all rectal cancer patients treated with the immunotherapy dostarlimab experienced a complete clinical response, meaning their tumors disappeared. This was the first time ever that a clinical trial had a 100% positive response rate.
thanks, i read reports of the study on jemperli and wanted to switch to it. asked my oncologist plus the second opinion doc at mayo phoenix. apparently i am pMMR though so they thought Herceptin was the better of the two. i was very impressed with the study results, however. the thing that bothers me is that i've had two medical people say, from looking at a very bad pre-surgery CT-scan and a clean one done post-fifth infusion, that it is obvious that the chemo is working. that seems like very bad logic - it seems to me that it means that either the surgery or the chemo is working. seems bad for them to base a treatment plan on bad logic. unless if i hadn't had the chemo, i would have metastasized by the second ct-scan BUT THEN WHY DIDN'T THEY SAY THAT WHEN I WAS TRYING TO DECIDE ON WHETHER TO DO CHEMO OR NOT????? these doctors are shifty little creatures -- JUST GIVE ME THE DATA!
thanks, i read reports of the study on jemperli and wanted to switch to it. asked my oncologist plus the second opinion doc at mayo phoenix. apparently i am pMMR though so they thought Herceptin was the better of the two. i was very impressed with the study results, however. the thing that bothers me is that i've had two medical people say, from looking at a very bad pre-surgery CT-scan and a clean one done post-fifth infusion, that it is obvious that the chemo is working. that seems like very bad logic - it seems to me that it means that either the surgery or the chemo is working. seems bad for them to base a treatment plan on bad logic. unless if i hadn't had the chemo, i would have metastasized by the second ct-scan BUT THEN WHY DIDN'T THEY SAY THAT WHEN I WAS TRYING TO DECIDE ON WHETHER TO DO CHEMO OR NOT????? these doctors are shifty little creatures -- JUST GIVE ME THE DATA!
Can I ask some questions to clarify what's going on? In one of your earlier posts, I think you said that your cancer was stage 4B. Is that right? That would mean that in the scan before your surgery, there would have been metastatic cancer outside of where they were going to operate. Right? Do you know where that was? Presumably that was not removed in your surgery? And did the report from the scan after some chemo say that those tumors had shrunk or disappeared? Do you have the radiology reports? They're usually pretty detailed about things like that.
At the two hospitals where I've had scans done, they also provide a link to the actual scans, which I find interesting to look through, although I'm not very good at spotting the cancer. But they often circle the tumors (in just one of the thousands of sections), so you can see what they're looking at.
I'm not a doctor, but from my perspective, it sounds like you're getting treatment that is better than standard of care, since you're getting the Herceptin.
Thank you so very much for the clarification. I want to get on Herceptin/trastuzumab because my HER 2 score is 3+ , the worst. Insurance wouldn't approve it and won't until other treatments have proved useless. Right now I have "mixed results." My oncologist tried hard to get it for me, and also appealed to the drug company for compassionate freebie, but no luck. The justification for denial is that it isn't yet approved for uterine cancer - just breast cancer. I have Untited Health Medicare. Would love to hear from others if you got approved for Herceptin/trastuzumab with your insurance, and what insurance you have. Maybe I could use that to make an appeal. "All these other companies approve it, so join the club." I haven't seen PD-1 on my lab report. I'll look again. There is a study on using Ivermectin against PD one at Cedar Sinai in LA . Not sure how it worked out. Any know anything about Ivermectin use? It doesn't cost much so there isn't any incentive for drug companies to spend a lot of dollars to study it. No return on investment. If I'm pMMR how does that connect with PD -1, if at all?
Here's an explanation of how anti-PD-1 drugs work. It's probably TMI.
PD-1 is a protein found on the surface of immune cells (not cancer cells). When the immune cell is in position to kill a target cell, PD-1 can bind to a protein on the surface of the target cell called PD-L1 and this prevents the killing. So expressing PD-L1 is one way that cancer cells escape killing by the immune system. Keytruda, Jemperli, and several similar drugs prevent the PD-1 to PD-L1 interaction and restore killing of cancer cells by immune cells.
But there's something else needed for the immune system to want to kill the cancer cells in the first place. It has to recognize the cancer cells as abnormal. The main way this happens is because the cancer has mutations, some of which cause it to make abnormal proteins. The immune system can detect these abnormal proteins.
Some cancers have thousands of mutations and so make thousands of abnormal proteins that can generate an immune response. Other cancers only have a few mutations. So using Keytruda etc. to unleash the immune system works much, much better on cancers with lots of mutations. Cancers that are defective in the DNA repair process called mismatch repair (MMR) have lots of mutations. So do cancers with mutations in the gene POLE, as well as melanomas (which have uv-induced mutations) and lung cancers, particularly in smokers. So Keytruda etc can have dramatic effects on these cancers.
Endometrial cancers that are proficient in MMR (pMMR) tend not to have many mutations, so there's not a high likelihood of a major response to Keytruda or Jemperli. They do give them to people anyway, since there is a modest improvement in prognosis with them.
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Thank you for sharing your journey and the helpful links. Love the foreign travel. Up yours, cancer! You go girl. Carpe Diem!
If you are dmmr have you seen the big news article from Sloan Kettering that was in the New England Journal of Medicine? It was on regular news outlets, too. The problem with the mismatch repair allowed the drug to target and strip cancer cells of protection and be DESTROYED. Here's the article . Dostarlimab is the drug they used.
The New England Journal of Medicine published a paper on April 27, 2025, that presents exciting new results from a clinical trial led by Memorial Sloan Kettering Cancer Center (MSK) gastrointestinal oncologists Andrea Cercek, MD, and Luis Diaz Jr., MD, that demonstrates how immunotherapy alone can help patients with MMRd cancers avoid surgery and preserve their quality of life. The results, presented simultaneously at the 2025 American Association of Cancer Research (AACR) Annual Meeting, showed that 80% of patients with several types of cancer treated with immunotherapy did not require surgery, radiation, or chemotherapy after six months of treatment with immunotherapy alone. Swim Across America awarded grants for the early-stage research and continues to award grants for the ongoing clinical trial.
Andrea Cercek, M.D., gastrointestinal oncologist and co-director of the Center for Young Onset Colorectal and Gastrointestinal Cancer at Memorial Sloan Kettering Cancer Center
Mismatch repair deficiency (MMRd) in cancer refers to a situation where tumor cells have defective mismatch repair (MMR) proteins, essential for correcting DNA errors during cell replication. This deficiency leads to the accumulation of mutations, including microsatellite instability (MSI), making tumors more prone to be recognized by the immune system. MMRd status is a significant factor in cancer treatment, particularly for immunotherapy, as it can predict response to immune checkpoint inhibitors.
The standard of care for many cancers that have this specific MMRd genetic mutation has been surgery, radiation, and chemotherapy. Still, the patients who responded positively to this clinical trial did not require surgery to remove an organ and did not experience chemotherapy or radiation, which improved their quality of life. This trial is the first time that immunotherapy has been shown to replace surgery for a variety of solid tumors.
“This study shows that immunotherapy can replace surgery, radiation and chemotherapy for mismatch repair-deficient solid tumors, which could help patients preserve their organs and avoid the harsh side effects of chemo and radiation,” said Andrea Cercek, M.D., gastrointestinal oncologist and co-director of the Center for Young Onset Colorectal and Gastrointestinal Cancer at Memorial Sloan Kettering Cancer Center. “Preserving a patient’s quality of life, while also successfully achieving positive results in eliminating their cancer, is the best possible outcome. They can return to their daily routines and maintain their independence.”
Luis Diaz, M.D., gastrointestinal oncologist and Head of the Division of Solid Tumor Oncology at Memorial Sloan Kettering Cancer Center
This phase 2 trial is an extension of a groundbreaking study, also funded in part by Swim Across America, in which all rectal cancer patients treated with the immunotherapy dostarlimab experienced a complete clinical response, meaning their tumors disappeared. This was the first time ever that a clinical trial had a 100% positive response rate.
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2 ReactionsDefinitely save those hair accessories!
My hair grew back in a mop and I had it shaped up into a short style about 5 months after my last chemo. For whatever it’s worth, I kept it short and ditched the hair dryer & straightener. Very freeing and a time saver as well.
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Like -
Helpful -
Hug
4 ReactionsChemo is kind of awful = but for most of us being alive is so worth it! Hard decisions.
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1 ReactionThis is great news for many women with aggressive cancers. Sadly, my biomarker report card says that I’m proficient, but maybe there will soon be something equally hopeful for me and my sisters soon.
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Helpful -
Hug
2 ReactionsThank you so very much for the clarification. I want to get on Herceptin/trastuzumab because my HER 2 score is 3+ , the worst. Insurance wouldn't approve it and won't until other treatments have proved useless. Right now I have "mixed results." My oncologist tried hard to get it for me, and also appealed to the drug company for compassionate freebie, but no luck. The justification for denial is that it isn't yet approved for uterine cancer - just breast cancer. I have Untited Health Medicare. Would love to hear from others if you got approved for Herceptin/trastuzumab with your insurance, and what insurance you have. Maybe I could use that to make an appeal. "All these other companies approve it, so join the club." I haven't seen PD-1 on my lab report. I'll look again. There is a study on using Ivermectin against PD one at Cedar Sinai in LA . Not sure how it worked out. Any know anything about Ivermectin use? It doesn't cost much so there isn't any incentive for drug companies to spend a lot of dollars to study it. No return on investment. If I'm pMMR how does that connect with PD -1, if at all?
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Helpful -
Hug
2 Reactionsive got basic medicare w aarp medigap g. love it. basically if medicare approves it, medigap pays the copay. basic medicare has no maximum out of pocket which is VERY bad but the additional medigap does. have to get your own drug policy tho
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3 ReactionsThank you! My doc said something about a cousin drug to Traszumabab that I could take if the chemo I'm on doesn't work. I bet this is it. Wish I didn't have to wait. I'll ask her about Enhertu.
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Like -
Helpful -
Hug
1 Reactionthanks, i read reports of the study on jemperli and wanted to switch to it. asked my oncologist plus the second opinion doc at mayo phoenix. apparently i am pMMR though so they thought Herceptin was the better of the two. i was very impressed with the study results, however. the thing that bothers me is that i've had two medical people say, from looking at a very bad pre-surgery CT-scan and a clean one done post-fifth infusion, that it is obvious that the chemo is working. that seems like very bad logic - it seems to me that it means that either the surgery or the chemo is working. seems bad for them to base a treatment plan on bad logic. unless if i hadn't had the chemo, i would have metastasized by the second ct-scan BUT THEN WHY DIDN'T THEY SAY THAT WHEN I WAS TRYING TO DECIDE ON WHETHER TO DO CHEMO OR NOT????? these doctors are shifty little creatures -- JUST GIVE ME THE DATA!
-
Like -
Helpful -
Hug
1 ReactionCan I ask some questions to clarify what's going on? In one of your earlier posts, I think you said that your cancer was stage 4B. Is that right? That would mean that in the scan before your surgery, there would have been metastatic cancer outside of where they were going to operate. Right? Do you know where that was? Presumably that was not removed in your surgery? And did the report from the scan after some chemo say that those tumors had shrunk or disappeared? Do you have the radiology reports? They're usually pretty detailed about things like that.
At the two hospitals where I've had scans done, they also provide a link to the actual scans, which I find interesting to look through, although I'm not very good at spotting the cancer. But they often circle the tumors (in just one of the thousands of sections), so you can see what they're looking at.
I'm not a doctor, but from my perspective, it sounds like you're getting treatment that is better than standard of care, since you're getting the Herceptin.
-
Like -
Helpful -
Hug
1 ReactionHere's an explanation of how anti-PD-1 drugs work. It's probably TMI.
PD-1 is a protein found on the surface of immune cells (not cancer cells). When the immune cell is in position to kill a target cell, PD-1 can bind to a protein on the surface of the target cell called PD-L1 and this prevents the killing. So expressing PD-L1 is one way that cancer cells escape killing by the immune system. Keytruda, Jemperli, and several similar drugs prevent the PD-1 to PD-L1 interaction and restore killing of cancer cells by immune cells.
But there's something else needed for the immune system to want to kill the cancer cells in the first place. It has to recognize the cancer cells as abnormal. The main way this happens is because the cancer has mutations, some of which cause it to make abnormal proteins. The immune system can detect these abnormal proteins.
Some cancers have thousands of mutations and so make thousands of abnormal proteins that can generate an immune response. Other cancers only have a few mutations. So using Keytruda etc. to unleash the immune system works much, much better on cancers with lots of mutations. Cancers that are defective in the DNA repair process called mismatch repair (MMR) have lots of mutations. So do cancers with mutations in the gene POLE, as well as melanomas (which have uv-induced mutations) and lung cancers, particularly in smokers. So Keytruda etc can have dramatic effects on these cancers.
Endometrial cancers that are proficient in MMR (pMMR) tend not to have many mutations, so there's not a high likelihood of a major response to Keytruda or Jemperli. They do give them to people anyway, since there is a modest improvement in prognosis with them.
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Like -
Helpful -
Hug
5 Reactions