“”Cause sometimes you just feel tired,Feel weak, and when you feel weak, you feel like you wanna just give up. But you gotta search within you, you gotta find that inner strength. And just pull that … out of you and get that motivation to not give up. And not be a quitter, no matter how bad you wanna just fall flat on your face and collapse” – Eminem
Lately it seems like nothing is going my way. I wanted to blog earlier but I got sick. Sadly I had to skip church and T’s rugby tournament because I just felt like crap. I wouldn’t say I am the most religious but I am spiritual and it feels good to be there. I want to get better so I can bake for the people there and participate in the activities. I can no longer sing as I am having trouble talking and coughing. I have a build up of phlegm that makes eating and drinking difficult as the constant tickle makes me gag.
Speaking of eating, I am contemplating discontinuing the diet. I haven’t seen improvement but I do like the sense of control it gives me. Depending on my platelet count I will start the next chemo soon but my doctor has suggested reconsidering reradiation. It’s a risky decision as there’s a 15% chance of paralysis due to necrosis. I just want to celebrate my 21 after enjoying Halloween. November 11 marks one year since diagnosis and is my birthday.
In other news I am now a fan of iced coffee and can’t be more like a middle aged woman. Plus, my mom and I have started going to matinees once a week so it’s us and the old people. We saw A Walk in the Woods (if I ever have 6 months to kill I would love to hike the Appalachian Trail), The Intern, and Pan. I have a huge movie list and am currently working on Batman; I loved the X-Men series. Netflix also definitely needs to create another Longmire season to tie up some loose ends.
CHOP is thinking about starting an integrative oncology therapy program that would include aromatherapy, acupuncture, acupressure, chiropractic therapy, yoga, tai-chi, among others. I am very interested in these complimentary treatments. I am also very interested in cannabis oil if the next chemo doesn’t work. I just feel like I am running out of options. With worsening balance, life is getting harder and it feels like it doesn’t want me to win. I try to stay positive but it’s hard at times. I recently read an interesting article ar St. Baldrick’s that is about a new possible treatment.
Shane and Tutka have been coming over for American Horror Story and football and it feels good to not be forgotten. Speaking of which, I have not forgotten about my girls as I tried to see most of them play.
I learned Texas Hold ‘Em so prepare to lose some money around me. It still has nothing on Yahtzee.
I have been ordering funny cancer shirts and my doctor loved the one that said “my oncologist does my hair.”
Two songs that make me emotional are “Fight Song” by Rachel Platten and “Leave Out All the Rest” by Linkin Park. I love the October weather and just hope to experience it again. I miss Quinnipiac and try to keep up on Q30 TV, The Chronicle, Facebook, Twitter, and just started using Instagram. I really want to be there for my friends’ birthdays. I also recently got a stationary bike to get some more movement and boy is it tiring. Well less than a month until my birthday so here’s hoping to a stronger month.
Inoperable 
Nathan. I am a colleague of your Dads at work. Keep on fighting! My family and I are praying for you. Your blog is amazing and it has inspired me during difficult times. We are all here for you!
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My dear Nathan I know you had better days and I see and feel your frustration ,but you determination and inner strength are bigger than the tumor. You are always in my thoughts and I my prayers you are never forgotten. Let me know when you decide to stop the diet puertorrican surtirlos are coming your way with the sauce you love. Can’t wait to celebrate your birthday ❤️ love you Natha Orsini
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So sad to hear that it’s been such a struggle recently. Thinking of you every day and sending many prayers your way.
You are amazing and inspiring!
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Thanks for the blog. I am bummed that life isn’t going the way you want it to. But I am with you… push away the thought of giving up. There is a quote block on my kitchen window sill. I read it every day to remind myself of how much can positively change in a day. It says, “Just when the catapillar thought the world was over it became a butterfly.” Never give up. Life can surprise you in the most amazing ways. I’ll be there to celebrate your 21st with you!
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Nathan, so glad to hear from you. I work with Steve Swanson. I pray for you at church on Sunday, so I have you covered if you cannot get there. Stay strong your faith and strength will help you. Lenor
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Thank you Nathan for sharing all your feelings in this blog…the good as well as the very bad. You are remarkable and brave beyond belief and I admire your strength and courage. It is OK to feel tired, just rest awhile.
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((hugs)) & prayers of strength for you.
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Nathan,
I work with your Uncle Steve and I find you so strong and inspiring, I pray for you always .
Bonnye
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“In other news I am now a fan of iced coffee and can’t be more like a middle aged woman. ” You know I love you Nathan but wtf! Love – your favorite Iced coffee loving middle aged woman in Vermont (PS. I’ll be there to celebrate 21!) XOXO
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Hey you should be honored I’m joining the group!
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You are a strong and brave young man Nathan. You are on our minds everyday ( you really truly are!!) you are not forgotten and you never will be. You are awe inspiring. We hope to get up to NJ soon and have a visit. Until then keep up that Yahtzee game with Mr Turney.
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Nathan you should really look into the cannabis oil I have been researching it and it seems very promising, even if you have to go to another state to legally receive the treatment.
My mother and I both keep you in our prayers, your strength is really an inspiration to us all
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You’re an inspiration to so many and you probably are completely unaware of it. During this past year I have had some struggles myself. And when I say struggles, I mean “first world problems”. But sometimes even those seemingly trivial things are not trivial to me.
When I feel down, I will think of you and your family. Your positive attitude and enduring hope is such an inspiration. You have been my teacher. Thank you for showing me how to stay positive under any circumstance.
You have also introduced my to music that I would never have known. And for that I’m eternally grateful.
“You gotta fight for your right to party” -Beastie Boys.
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Nathan, You are strong and amazing. You are smart beyond your years. You are an inspiration to me and my family. You give me and others the courage to take on anything. You Nathan are in my prayers every day as you work through these difficult time’s.
Much love the Kennedy family.
Mr. K
Sent from my Windows Phone ________________________________
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Nathan, you’ve always been such a hard worker and I can see that is why you are not giving up. This is Señora Tominac, your middle school Spanish teacher. Maintain your positive attitude and enjoy all those movies with your mom 🙂 You are in my prayers 🙂
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Dear Nathan,
I am praying for you and your family. My friend D’Anne is a friend of your mom and shared your blog with me. Praying that you can lean in on Jesus for strength and security that He walks with you hand in hand through it all.
Come to Me, all you who are weary and burdened, and I will give you rest. Take My yoke upon you and learn from Me, for I am gentle and humble in heart, and you will find rest for your souls. For My yoke is easy and My burden is light. — Matthew 11:28-30
The cannabis oil has helped some friends but the taste is foul so they used capsules or suppositories.
We go to Dana Farber for our son and I have an article that I found very encouraging about a trailer hitch form of delivery for killing off the proteins in the cancer cells rapidly and completely. In the article it ends with ready to find a marketing company. I hope they could help as well. Blessings,
Mel
New chemical technology boosts potency of targeted cancer therapy
May 21, 2015
Tags: BasicResearch, TargetedTherapy
James Bradner, MD
In work that heralds a new, more potent form of targeted therapy for cancer, Dana-Farber Cancer Institute scientists have devised a chemical technology that doesn’t just disable malevolent proteins in tumor cells, as current agents do, but destroys them.
As described in a study posted online May 21, 2015, by Science Express, the strategy uses tumor cells’ own protein-chopping machinery to break down and dispose of proteins that drive cancer growth. When tested in laboratory samples of leukemia cells and in animals with human-like leukemia, the approach caused cancer cells to die much more quickly than with conventional targeted therapies.
Researchers developed the strategy as a way to develop inhibitors of “undruggable” proteins and overcome drug resistance, a common shortcoming of targeted therapies. Resistance arises when tumors that originally responded to a particular therapy manage to circumvent the drug’s effects and resume their growth.
“One of the reasons resistance occurs is that cancer-related proteins often have multiple functions within the cell, and conventional targeted therapies inhibit just one or a few of those functions,” said the paper’s senior author, James Bradner, MD, an oncologist and chemist at Dana-Farber. “Conventional drugs allow the targeted protein to adapt to the drug, and the cell finds alternate routes for its growth signals.
“We began designing approaches that cause the target protein to disintegrate, rather than merely be inhibited,” he continued. “It would be very powerful if we could chemically convert an inhibitor drug into a degrader drug.”
Doing so would involve manipulating the cell’s natural protein-elimination system. Used-up or unneeded proteins are tagged for disposal by enzymes that attach a protein called ubiquitin to them. The marked proteins are then brought to a structure called the proteasome, where they’re ground up and recycled. Three enzymes — dubbed E1, E2, and E3 — collaborate to affix the tags.
To harness this system for the destruction of cancer proteins, Bradner’s team designed a chemical adapter that attaches to a targeted drug molecule. The adapter works like a tiny trailer hitch, enabling the drug to tow the cell’s protein-degradation machinery directly to the protein of interest. Once bound to that protein, the combination drug-and-protein-degrader essentially demolish it.
From left: Georg Winter, PhD, James Bradner, MD, and Dennis Buckley, PhD, led the research.
The team tested the technology — which they dubbed “degronimids” — in laboratory samples of leukemia cells. They began with the drug JQ1, which inhibits BRD4, a protein that orchestrates the expression of cancer growth genes. They built an adapter out of phthalimide — a chemical derivative of the drug thalidomide — and attached it to JQ1. The phthalimide was designed to bind snugly to a protein-degrading enzyme E3 (called Cereblon), making it ideal as a trailer hitch.
When investigators treated the leukemia cells with a JQ1-and-phthalimide “conjugate” called dBET1, the BRD4 protein within the cells was degraded in less than an hour. Such rapid and extensive degradation suggests that conjugates may be able to prevent or hinder cancer cells from developing resistance to targeted therapies, the researchers state.
“The potency, selectivity, and rapidity of this approach — namely the ability to home in specifically on BRD4 — are unprecedented in clinical approaches to protein degradation,” Bradner said.
To determine how selective dBET1 actually is, the researchers measured the levels of all proteins in leukemia cells one and two hours after treatment. “We were stunned to find that only three proteins of more than 7,000 in the entire cell were degraded: BRD2, 3, and 4, — an exceptional degree of selectivity guided by the intended targets of JQ1,” Bradner said. “It’s as though dBET1 is laser-guided to deliver protein-degrading machinery to targeted proteins.”
The investigators then tested dBET1 in mice bearing a widespread and aggressive form of human leukemia. As in the laboratory cell samples, there was a rapid degradation of BRD4 in the tumor cells and a powerful anti-leukemia effect, with few noticeable side effects.
To see if compounds other than JQ1 can be used as a guidance system for a conjugate, the researchers created a set of molecules that lock the protein-degradation machinery onto a compound called SLF, which targets a protein called FKBP12. When they treated cancer cells with SLF, they found it degraded the vast majority of FKBP12 in the cells within a few hours.
Buoyed by these results, Dana-Farber researchers are working to create a derivative of dBET1 that can be used as a drug in human patients — and to extend the conjugate strategy for the treatment of other cancers and other genetically-caused diseases.
“We’re very excited that this chemical technology may offer a way to improve many cancer drug molecules, and of course this strategy has implications beyond cancer for the treatment of other life-threatening diseases,” Bradner said.
“The dBET1 and the dFKBP12 compounds are presently in a late stage of lead optimization for therapeutic development in both cancer and non-malignant diseases,” says Prem Das, PhD, chief research business development officer at Dana-Farber. “Composition-of-matter and method-of-use patent applications have been filed on these and other additional targeted agents, as well as on the chemistry platform. They will be licensed for commercialization to an appropriate company according to standard Dana-Farber practice.” Potential partners or investors can contact Das at the Robert and Renée Belfer Office for Dana-Farber Innovations.
The lead authors of the paper are Georg Winter, PhD, and Dennis Buckley, PhD, of Dana-Farber. Co-authors are Joshiawa Paulk, PhD, Justin Roberts, Amanda Souza, and Sirano Dhe-Paganon, PhD, all of Dana-Farber.
The study was supported by philanthropic gifts from Marc Cohen and Alain Cohen, the William Lawrence and Blanche Hughes Foundation, and grants from the National Institutes of Health (numbers R01-CA176745 and P01-CA066996).
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Nathan – you are such an inspiration to many. You are always in our thoughts and prayers. Keep up the fight! You are the bravest young man that I know.
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Keep faith in you and in the light of God, You are strong , brave, blessings from heaven. Clara Turner
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there is nothing wrong with being a middle aged woman who loves Iced Coffee, of course I do not consider myself a middle aged woman just yet.
I will think of you whenever I hear “this is my fight song, take back my life song”
we stand strong with you Nathan. may you feel all the love that surrounds you. you truly are amazing. always thinking of you and your family- The cowell family
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Nathan,
I have been reading your blogs and just wanted to let you know to stay strong and keep fighting. You are a complete inspiration to my family and I.
-Colin
P.S. My little daughter Savannah says hi and loves seeing you on her walks around the block 🙂
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Tell her I say hi back and not to stop those walks!
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Hi Nathan! I am a member of Relay for Life at Loyola University Maryland. We are all rooting for you! We’re here for you and support you 110%! Keep on fighting!!
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Hi Nathan, I’ve been thinking of you as your birthday and the anniversary of your diagnosis nears. Just wanted to send you a note to let you know your Quinnipiac family misses you and holds you close in our hearts and prayers. Keep fighting Nathan and know you are surrounded by much love and support! Monique Drucker, VP & Dean of Students
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Hey cuz, this is your godfather. We miss you and think about you every day. The twins just turned 5, bigger every day, Sloan just got his first stitches. I’m exposing him to as much UEFA competition as possible, a little rugby, too. Can’t wait for us to all hang again. Love you so much, man . Your bravery is truly awe-inspiring. I have much to learn from you. Hang in there. Peace.
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Nathan, I have read about quite a bit of success with cannabis oil, especially with inoperable tumors….I have read it not only helps with decreasing symptoms, but also the actual cancer….I hope you can find the information you need about acquiring the oil, as I believe it is legal in NJ (coming soon everywhere :-). Essential oils are also extremely healing and I’m excited to read CHOP pursuing treatments beyond chemo and radiation, because I believe you will find your answers there! You are always in our thoughts and know that your persistence at finding a treatment that works for you will prevail!!! Fondly, Dria Miller (Kael’s Mom <3)
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