The Cure MTC Project: Stage I
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Medullary Thyroid Carcinoma (MTC) is a rare cancer originating from the calcitonin-secreting C cells of the thyroid. Unlike it's much more common counterpart, papillary thyroid cancer, there currently exists no cure for metastatic MTC. This is the beginning of mutli-pronged, patient-led effort to revolutionize treatment for MTC. In the current research thrust several novel drug combos will be evaluated in a mouse model. Despite it's rarity, there has been a great deal of fundamental research into the molecular drivers of MTC, providing a rationale to improve treatment paradigms beyond single-agent RET inhibitors Cometriq and Caprelsa.
The first is based on a 2010 paper from researchers at MD Anderson, which shows that RET inhibition alone is insufficient to prevent MTC cancer stem cells from proliferating in vitro. This partially explains resistance to single agent RET inhibtion. However, the researchers showed that by inhibiting three cancer related kinases RET/FGF/EGF, the cancer stem cells could be almost entirely prevented from proliferating. At the time, the researchers had to use a special technique called siRNA knockdown to silence these cancer-related cellular pathways. While such a technique works in a petri dish; it does not work well in vivo. Fortunately due to recent advancements in drug development, there are now drugs available that can inhibit all three (RET/EGF/FGF) in vivo. Thus, this novel novel approach to treating MTC will be evaluated in vivo for the first time, potentially paving the way for an improved treatment regimen. The drug combo of cabozantinib, AZD4547, and erlotinib will be tested in mice and compared to cabozantinib alone.
A second approach to treating MTC, which could potentially lead to complete responses, not just partial involves using the dual drug combo of capecitabine/temozolomide, also known as CapTem. Pioneeering work by Dr. Fine at Columbia has shown CapTem to be effective in some neuroendocrine tumors, leading to functional cures in several end-stage pituary tumor patients. (MTC is a neuroendocrine tumor). In parallel to this effort, reserachers have recently shown the pro-survival effects of constant RET activation in MTC cells. By having the "RET switch" jammed permanently, into the "ON" position, MTC cells are immortalized. It is therefore expected that by inhibiting RET, MTC will be susceptible to traditional forms of non cell cycle specific chemo that have worked well in other neuroendocrine cancers. The following drug combo of cabozantinib+CapTem will be tested in mice for the first time and will be compared to cabozantinib alone. It is anticipated that this regimen will lead to complete tumor regressions in mice.
These experiments represent Stage I in the research plan. Stage II will involve employing a customized peptide vaccine targeting overexpressed proteins in MTC. The vaccine will used alone, or in combination with the best drug combo found from Stage I. The vaccine will also be tested with an epigenetic modulator and immune checkpoint antibodies, such as LAG3, PD1, PDL1 , TIM3 or KIR. Stage II is much more expensive and time consuming and will require special RET genetically engineered mice. It will be launched immediately after Stage I is complete.
This research project is based on literally thousands of hours of personal reserach from a PhD/patient and dozens of hours of discussions with an esteemed MTC researcher, who also focuses on a number of other cancers such as GBM and thus has limited bandwidth to do solely MTC research.
The goal of this patient-led, crowd-funded effort is to accelerate treatments into clinical trials by establishing strong preclinical data and to ultimately cure MTC.
We are on the brink of a revolution in cancer care, but cancer is a tricky disease, so multi-modal therapy, including moleculary targeted drugs, vaccines, epigenetic modulators, immune checkpoing inhibitors and potentially traditional chemo may all have a role to play in achieving high cure rates.
This reserach project is one small piece of the puzzle, but it will enable rapid evaluation of promising preclinical leads. In the first of it's kind, all research data will be published in real-time. In the first of it's kind, unprecedented transparency will show those investing in this project where every single penny is spent, allowing a first-hand look at the actual cancer research project. Data will be provided as an official report from the in vivo contracting lab. Results will be written up and submitted to a respectable journal. I should mention that my collaborator at MD Anderson has already performed in vitro studies showing promising efficacy and I am thus extremely hopeful we will get promising results in vivo!
Your help on this journey will make a difference! All funding will go to paying for the mouse study. All results will be shared with a tenured professor at MD Anderson who plays a major role in shaping clinical trials, and of course the data can readily be shared with your doctors.
GoFundMe does not provide the best formatting, but a rough breakdown of drug costs is shown below. Documents with clear formatting will be provided on the Facebook site.
Kind regards,
Tim E
Drug # Mice Dose (mg/kg/day) #days Mouse Weight (kg) Amount needed (mg) Unit cost Roundup Quantity (mg) Total Drug Cost ($)
ponatinib (RET/FGF inhibitor) 1 30 30 0.04 36 $370/50mg 50 370
cabozantinib (RET/MET inhibitor) 9 20 30 0.04 216 $470/50mg [phone redacted]
celecoxib (COX2/AKT inhibitor) 3 25 30 0.04 90 $97/100mg 100 97
capecitabine (anti-metabolite) 3 50 20 0.04 120 $197/1000mg 1000 197
temozolomide (alkylating agent) 3 12 12 0.04 17.28 $70/25mg 25 70
erlotinib (EGFR inhibitor) 3 70 30 0.04 252 $370/500mg 500 370
AZD4547 (FGF inhibitor) 3 5 30 0.04 18 $170/10mg 20 340
*Drug Source: Selleckchem.com Total for all drugs $3,794
*Drugs sold in fixed quantities Total w/o cabozantinib $1,444
The first is based on a 2010 paper from researchers at MD Anderson, which shows that RET inhibition alone is insufficient to prevent MTC cancer stem cells from proliferating in vitro. This partially explains resistance to single agent RET inhibtion. However, the researchers showed that by inhibiting three cancer related kinases RET/FGF/EGF, the cancer stem cells could be almost entirely prevented from proliferating. At the time, the researchers had to use a special technique called siRNA knockdown to silence these cancer-related cellular pathways. While such a technique works in a petri dish; it does not work well in vivo. Fortunately due to recent advancements in drug development, there are now drugs available that can inhibit all three (RET/EGF/FGF) in vivo. Thus, this novel novel approach to treating MTC will be evaluated in vivo for the first time, potentially paving the way for an improved treatment regimen. The drug combo of cabozantinib, AZD4547, and erlotinib will be tested in mice and compared to cabozantinib alone.
A second approach to treating MTC, which could potentially lead to complete responses, not just partial involves using the dual drug combo of capecitabine/temozolomide, also known as CapTem. Pioneeering work by Dr. Fine at Columbia has shown CapTem to be effective in some neuroendocrine tumors, leading to functional cures in several end-stage pituary tumor patients. (MTC is a neuroendocrine tumor). In parallel to this effort, reserachers have recently shown the pro-survival effects of constant RET activation in MTC cells. By having the "RET switch" jammed permanently, into the "ON" position, MTC cells are immortalized. It is therefore expected that by inhibiting RET, MTC will be susceptible to traditional forms of non cell cycle specific chemo that have worked well in other neuroendocrine cancers. The following drug combo of cabozantinib+CapTem will be tested in mice for the first time and will be compared to cabozantinib alone. It is anticipated that this regimen will lead to complete tumor regressions in mice.
These experiments represent Stage I in the research plan. Stage II will involve employing a customized peptide vaccine targeting overexpressed proteins in MTC. The vaccine will used alone, or in combination with the best drug combo found from Stage I. The vaccine will also be tested with an epigenetic modulator and immune checkpoint antibodies, such as LAG3, PD1, PDL1 , TIM3 or KIR. Stage II is much more expensive and time consuming and will require special RET genetically engineered mice. It will be launched immediately after Stage I is complete.
This research project is based on literally thousands of hours of personal reserach from a PhD/patient and dozens of hours of discussions with an esteemed MTC researcher, who also focuses on a number of other cancers such as GBM and thus has limited bandwidth to do solely MTC research.
The goal of this patient-led, crowd-funded effort is to accelerate treatments into clinical trials by establishing strong preclinical data and to ultimately cure MTC.
We are on the brink of a revolution in cancer care, but cancer is a tricky disease, so multi-modal therapy, including moleculary targeted drugs, vaccines, epigenetic modulators, immune checkpoing inhibitors and potentially traditional chemo may all have a role to play in achieving high cure rates.
This reserach project is one small piece of the puzzle, but it will enable rapid evaluation of promising preclinical leads. In the first of it's kind, all research data will be published in real-time. In the first of it's kind, unprecedented transparency will show those investing in this project where every single penny is spent, allowing a first-hand look at the actual cancer research project. Data will be provided as an official report from the in vivo contracting lab. Results will be written up and submitted to a respectable journal. I should mention that my collaborator at MD Anderson has already performed in vitro studies showing promising efficacy and I am thus extremely hopeful we will get promising results in vivo!
Your help on this journey will make a difference! All funding will go to paying for the mouse study. All results will be shared with a tenured professor at MD Anderson who plays a major role in shaping clinical trials, and of course the data can readily be shared with your doctors.
GoFundMe does not provide the best formatting, but a rough breakdown of drug costs is shown below. Documents with clear formatting will be provided on the Facebook site.
Kind regards,
Tim E
Drug # Mice Dose (mg/kg/day) #days Mouse Weight (kg) Amount needed (mg) Unit cost Roundup Quantity (mg) Total Drug Cost ($)
ponatinib (RET/FGF inhibitor) 1 30 30 0.04 36 $370/50mg 50 370
cabozantinib (RET/MET inhibitor) 9 20 30 0.04 216 $470/50mg [phone redacted]
celecoxib (COX2/AKT inhibitor) 3 25 30 0.04 90 $97/100mg 100 97
capecitabine (anti-metabolite) 3 50 20 0.04 120 $197/1000mg 1000 197
temozolomide (alkylating agent) 3 12 12 0.04 17.28 $70/25mg 25 70
erlotinib (EGFR inhibitor) 3 70 30 0.04 252 $370/500mg 500 370
AZD4547 (FGF inhibitor) 3 5 30 0.04 18 $170/10mg 20 340
*Drug Source: Selleckchem.com Total for all drugs $3,794
*Drugs sold in fixed quantities Total w/o cabozantinib $1,444
Organizer
Timothy Erickson
Organizer
