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- cross-posted to:
- technews@radiation.party
- technology@lemmy.ml
City of Hope scientists develop targeted chemotherapy able to kill all solid tumors in preclinical research
www.cityofhope.orgThe City of Hope-developed investigational small molecule selectively disrupts DNA replication and repair in cancer cells, leaving healthy cells unaffected, a new study reports. CONTACT Zen Logsdon 626-409-9367zlogsdon@coh.org The City of Hope-developed small molecule AOH1996 targets a cancerous variant of the protein PCNA. In its mutated form, PCNA is critical in DNA replication and repair of all expanding tumors. Here we see untreated cancer cells (left) and cancer cells treated with AOH1996 (right) undergoing programmed cell death (violet). (Photo credit: City of Hope)LOS ANGELES — Researchers at City of Hope, one of the largest cancer research and treatment organizations in the United States, today published a new study explaining how they took a protein once thought to be too challenging for targeted therapy, proliferating cell nuclear antigen (PCNA), and developed a targeted chemotherapy that appears to annihilate all solid tumors in preclinical research. As the scientists continue to investigate the foundational mechanisms that make this cancer-stopping pill work in animal models, they note that there is an ongoing Phase 1 clinical trial testing the City of Hope-developed therapeutic in humans. Most targeted therapies focus on a single pathway, which enables wily cancer to mutate and eventually become resistant, said Linda Malkas, Ph.D., professor in City of Hope’s Department of Molecular Diagnostics and Experimental Therapeutics and the M.T. & B.A. Ahmadinia Professor in Molecular Oncology. However, the cancer-killing pill Malkas has been developing over the past two decades, AOH1996, targets a cancerous variant of PCNA, a protein that in its mutated form is critical in DNA replication and repair of all expanding tumors. “PCNA is like a major airline terminal hub containing multiple plane gates. Data suggests PCNA is uniquely altered in cancer cells, and this fact allowed us to design a drug that targeted only the form of PCNA in cancer cells. Our cancer-killing pill is like a snowstorm that closes a key airline hub, shutting down all flights in and out only in planes carrying cancer cells,” said Malkas, senior author of the new study published in Cell Chemical Biology today. “Results have been promising. AOH1996 can suppress tumor growth as a monotherapy or combination treatment in cell and animal models without resulting in toxicity. The investigational chemotherapeutic is currently in a Phase 1 clinical trial in humans at City of Hope.” AOH1996 has been effective in preclinical research treating cells derived from breast, prostate, brain, ovarian, cervical, skin and lung cancers and is exclusively licensed by City of Hope to RLL, LLC, a biotechnology company that Malkas co-founded and holds financial interest in. The researchers tested AOH1996, a small molecule PCNA inhibitor, in more than 70 cancer cell lines and several normal control cells. They found that AOH1996 selectively kills cancer cells by disrupting the normal cell reproductive cycle. It targets something called transcription replication conflicts, which occur when mechanisms responsible for gene expression and genome duplication collide. The investigational therapy prevented cells with damaged DNA from dividing in G2/M phase and from making a copy of faulty DNA in S phase. As a result, AOH1996 caused cancer cell death (apoptosis), but it did not interrupt the reproductive cycle of healthy stem cells. “No one has ever targeted PCNA as a therapeutic because it was viewed as ‘undruggable,’ but clearly City of Hope was able to develop an investigational medicine for a challenging protein target,” said Long Gu, Ph.D., lead author of the study and an associate research professor in the Department of Molecular Diagnostics and Experimental Therapeutics at Beckman Research Institute of City of Hope. “We discovered that PCNA is one of the potential causes of increased nucleic acid replication errors in cancer cells. Now that we know the problem area and can inhibit it, we will dig deeper to understand the process to develop more personalized, targeted cancer medicines.” Interestingly, experiments showed that the investigational pill made cancer cells more susceptible to chemical agents that cause DNA or chromosome damage, such as the chemotherapy drug cisplatin, hinting that AOH1996 could become a useful tool in combination therapies as well as for the development of new chemotherapeutics. “City of Hope has world leaders in cancer research. They also have the infrastructure to drive translational drug discovery from the laboratory into the clinic for patients in need,” said Daniel Von Hoff, M.D., study co-author and a distinguished professor at Translational Genomics Research Institute, part of City of Hope. City of Hope’s groundbreaking translational research history includes developing the technology underlying synthetic human insulin, a breakthrough in diabetes management, and monoclonal antibodies, which are integral to widely used, lifesaving cancer drugs, such as trastuzumab, rituximab and cetuximab. As a next step, the researchers will look to better understand the mechanism of action to further improve the ongoing clinical trial in humans. Individuals interested in the Phase 1 clinical trial should review the eligibility requirements at clinicaltrials.gov. If eligible, call 626-218-1133 or visit City of Hope’s clinical trials webpage. # # # The Cell Chemical Biology study entitled “Small Molecule Targeting of Transcription-Replication Conflict for Selective Chemotherapy” was supported by the Department of Defense (W81XWH-11-1-0786, W81XWH-19-1-0326 under BC181474 and BC181474P1), National Institutes of Health/National Cancer Institute (R01 CA121289, R01 CA225843), St Baldrick's Foundation, the Alex Lemonade Stand Foundation, Tobacco-Related Disease Research Program (TRDRP-T31IP626), Melanoma Research Foundation (MRF-717178), the ANNA Fund, RDL Foundation, Analytical Pharmacology Core supported by the National Cancer Institute of the National Institutes of Health (P30CA033572). About City of Hope City of Hope's mission is to deliver the cures of tomorrow to the people who need them today. Founded in 1913, City of Hope has grown into one of the largest cancer research and treatment organizations in the U.S. and one of the leading research centers for diabetes and other life-threatening illnesses. City of Hope research has been the basis for numerous breakthrough cancer medicines, as well as human synthetic insulin and monoclonal antibodies. With an independent, National Cancer Institute-designated comprehensive cancer center at its core, City of Hope brings a uniquely integrated model to patients spanning cancer care, research and development, academics and training, and innovation initiatives. City of Hope’s growing national system includes its Los Angeles campus, a network of clinical care locations across Southern California, a new cancer center in Orange County, California, and treatment facilities in Atlanta, Chicago and Phoenix. City of Hope’s affiliated group of organizations includes Translational Genomics Research Institute and AccessHopeTM. For more information about City of Hope, follow us on Facebook, Twitter, YouTube, Instagram and LinkedIn.
Ongoing clinical trial testing therapeutic in humans.
People downvote but it’s true. Most cancer can already be cured if we detect it early, and we have many early detection methods that go un-used because it costs insurance companies more. The scientific/medical arguments against routine screening are weak and pathetic.
Imagine a country where everyone over 40 gets an annual chest x-ray, and CT scans for smokers/former smokers.
Join us in the frozen North. I was three months out from a “scope” to look for colon cancer and my GP had a consult with me on an unrelated matter. He made a frowny face and said “you need another scope”. I told him I just had one. He insisted. So I went. Was on an operating table about four weeks later. I would have been dead without that scope. I had no problem doing that first or second scope because they were “free” (I am guessing about $1300 a year goes from my taxes to health care, so not free, just a decent price considering I have colleagues in the US where that won’t even cover two months).
That is far less than the average American insurance plan and those include co-pays and deductibles. I hate living in the U.S.
My wife and I each pay a little into our work health plans but that’s mostly to cover dental and a few other things we really don’t use.
Here’s an example of that coverage: I pay about $20 a month into my work plan. That covers pretty much all our dental work.
I occasionally have to pay out of pocket for some stuff (CPAP machine, dental implant) but get compensated after submitting paperwork (no deductible).
I worked in the US for a bit in a kitchen and was always worried about getting injured. At the time I couldn’t buy muscle relaxant over the counter which I thought was nuts (I get back spasms) until I realized requiring a prescription was one more was to squeeze people for a doctor’s visit.
You are aware, that you can get cancer caused by the radiation of these diagnostics?
That’s not completely true. Look up the video medlifecrisis did on it for just one example. When cancer isn’t cancer or epidemic of fake disease.
Part of the reason I consider those arguments weak, is we could be dedicating research money to solving those problems, but we don’t. In his video, he also is very quickly glossing over the counter points. For example, the patient who received a heart stent because they detected early narrowing of an artery would not be given a stent today, and instead it would be monitored, which is a good thing. For the breast cancer bit, two paragraphs show up on the screen showing a study that followed women with DCIS. 5/28 of those women died of breast cancer. So by the numbers in that study, testing positive means you would have an 18% chance of dying from breast cancer if you did nothing. Idk about you, but if my ods were practically 1 in 5 I’d be monitoring the situation. Again in the anecdote the patient chose to operate too early, and a good doctor would be advising against that. Lead time bias is the only argument I think isn’t weak, but there also isn’t really enough data on it for us to know for sure. That and the fact that deaths to cancer remains steady instead of going down as diagnosis goes up. I still think it would be better to screen people and monitor them if they test positive rather than wait for symptoms, because so often the symptoms come far too late. I also think more research could be done to reduce false positives and understand what makes some cancer not deadly. It’s severely under funded research because it doesn’t make money and it isn’t glamorous, but it could absolutely save lives
I agree there’s more money in just treating symptoms and EOL care than actually eradicating cancer, but future treatment/eradication is certainly glamorous. Just think of all the celebrities that keep dying from cancer that could come out and say I was saved by X.
Patric Swayze, Steve Jobs, David Bowie and Peewee Herman just to name a few.
Steve Jobs died because he tried homeopathic treatment the second time, so you can take him off that list lol.
Would he go the crazy route is there was an established treatment with 100% success rate though?
How many people you know that drink diluted shit to treat rabies? You just go get your shots like a good boy and live to get bit another day.
I mean, the treatment he had the first time worked, seems to me like it would make sense to do it again, especially with the advances in the treatment since the first time
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It’s not that bold, it’s something people have been saying for a long time. It’s been hotly debated for years, and there’s plenty of articles and YouTube videos discussing it
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I was trying to politely say go look it up yourself and form your own opinion
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