City of Hope scientists develop targeted chemotherapy able to kill all solid tumors in preclinical...
09/09/2023
[ad_1] The City of Hope-developed small molecule AOH1996 targets a
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Transparent mouse could improve cancer drug tests
05/09/2023
[ad_1]  A new scanning method involving a see-through mouse could
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Cannabis Effective at Reducing Symptoms in Children With Cancer, but More Research Needed
01/09/2023
[ad_1] Children with cancer who suffer from multiple symptoms related
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Study Takes Step Toward Treating Chemotherapy-Resistant Prostate Cancer
28/08/2023
[ad_1] Prostate cancer is a leading cause of death among
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New AI drug discovery collaboration aims to design new precision cancer drugs
24/08/2023
[ad_1]  Researchers are set to to combine expertise in drug
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Study explores the use of existing medicines to revolutionize cancer treatment
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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)

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 ‘Conference-registration-gbp/”>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 Award-call-for-profile/”>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 Award-call-for-profile/”>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).

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oncology.pencis.com/” target=”_blank”>A new scanning method involving a see-through mouse could improve how cancer drugs are tested, by picking up tumours previously too small to detect.

oncology.pencis.com/” target=”_blank”>Prof Ali Ertürk of the Helmholtz Munich Research centre worked out how to make a dead mouse transparent in 2018.

oncology.pencis.com/” target=”_blank”>His team have now used chemicals to highlight specific tissues so that they can be scanned in unprecedented detail.

oncology.pencis.com/” target=”_blank”>drugs are often tested first on mice. Scientists say the new scanning method could revolutionise medical Research.

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oncology.pencis.com/” target=”_blank”>cancer Research UK said the new scanning technique had “a wealth of potential”.

oncology.pencis.com/” target=”_blank”>The researchers say the method reveals far greater detail than existing scanning techniques. In one of the first applications the team has detected cancerous tumours in the first stages of formation.

oncology.pencis.com/” target=”_blank”>Prof Ertürk says this is important because cancer drugs have to be shown to eliminate tumours in mice before being tested on humans.

oncology.pencis.com/” target=”_blank”>”MRI and PET scans would show you only big tumours. Ours show tumours at the single cell, which they absolutely can’t”.

oncology.pencis.com/” target=”_blank”>”Current drugs extend life by a few years and then the cancer comes back. This is because the development process never included eliminating those tiny tumours, which were never visible.”

oncology.pencis.com/” target=”_blank”>Normally lab mice are given cancer and scanned with conventional scans to see how the tumour has progressed. They are then treated with the cancer drug being tested and then scanned again to see what if any difference the treatment has had.

oncology.pencis.com/” target=”_blank”>Prof Ertürk’s scanning method can only be used on dead mice, to give a picture of how much cancer has progressed, or potentially, whether a treatment has worked. He made mice transparent after they were given cancer and then scanned them using his new technique. Only a few mice would need to be made transparent to test the effectiveness of the drug.

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oncology.pencis.com/” target=”_blank”>Dr Rupal Mistry, Research information manager at cancer Research UK, said:

oncology.pencis.com/” target=”_blank”>”This exciting and unique scanning technique has a wealth of potential for building our knowledge of how our bodies work and what goes wrong in diseases like cancer.

oncology.pencis.com/” target=”_blank”>”While researchers will only be able to use the technique to examine the bodies of deceased mice, it could tell us a lot about how cancer develops at the early stages of the disease. Being able to visualise tumours in the context of the entire body will also give researchers a greater understanding of the impact of different drugs and treatment.

oncology.pencis.com/” target=”_blank”>”Advances in technology like this are essential to driving progress and will hopefully lead to new ways to detect, treat and prevent cancer.”

oncology.pencis.com/” target=”_blank”>The cancer application, published in the journal Nature Biotechnology, is just one of hundreds if not thousands to which the new scanning technique can be used to improve medical studies. It can enable researchers to see things they have never seen before.

oncology.pencis.com/” target=”_blank”>Mouse studies are often the starting point for learning about processes in the human body. But the new technique can be used on any animals. It could also be used to make human tissues and organs transparent, though it is unlikely to be used to make an entire human body transparent in the near future because there would be no medical advances that could be made from it at this stage.

oncology.pencis.com/” target=”_blank”>Creation of the transparent mouse involves removing all the fats and pigment from its corpse, using a chemical process. It ends up looking like a clear plastic toy, which is ever so slightly bendy. Its organs and nerves are all still inside it – but near invisible.

oncology.pencis.com/” target=”_blank”>While Prof Ertürk’s developed the process to make a mouse transparent five years ago, the scanning technique makes the most of it.

oncology.pencis.com/” target=”_blank”>He has found a way of adding other chemicals known as antibodies to highlight the parts of the mouse he is interested in studying under a microscope. Different antibodies stick to different types of tissue and so highlight whatever the researchers are interested in looking at.

oncology.pencis.com/” target=”_blank”>As well as highlighting cancerous areas, Prof Ertürk’s team has produced a suite of Videos which enable researchers to fly through the mouse’s nervous system, gut or lymph system.

oncology.pencis.com/” target=”_blank”>The scans have several advantages over what is available now.

oncology.pencis.com/” target=”_blank”>First, the researchers can study diseases in the context of the entire body, which gives them a much greater understanding of the impact of different drugs and treatments.

oncology.pencis.com/” target=”_blank”>The 3D images are also stored online, so researchers studying different parts of the animal or wanting to do the same experiment can draw from a library, rather than having to use another mouse. Prof Ertürk believes that the technique could reduce lab animal use tenfold.

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oncology.pencis.com/” target=”_blank”>Dr Nana-Jane Chipampe, of the Wellcome Sanger Institute in Cambridge, is excited at the prospect of using the new scanning technique to study how cells develop in the human body. Currently she has to slice up tissues into very thin sections to study them under a microscope. Soon she will be able to see details in 3D.

oncology.pencis.com/” target=”_blank”>”I can’t wait to get my hands on it!” she told me enthusiastically.

oncology.pencis.com/” target=”_blank”>”It has the potential to identify new tissues, cells and diseases which will really help us understand the development of diseases.”

oncology.pencis.com/” target=”_blank”>Her team leader, Prof Muzlifah Haniffa, is producing an online map or atlas of every cell in the human body. She says the new scanning technique will be useful for all kinds of medical Research.

oncology.pencis.com/” target=”_blank”>”Without a doubt, it will accelerate the pace of medical Research,” she said. “Combining these cutting-edge technologies and building the human cell atlas will no doubt completely revolutionise medicine.”

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oncology.pencis.com/” target=”_blank”>Children with cancer who suffer from multiple symptoms related to the disease and its treatment can benefit from the use of cannabis, but more Research needs to be done on correct dosing and safety, according to a recent study published in the journal cancer.1

oncology.pencis.com/” target=”_blank”>Survival rates in childhood cancer have significantly improved thanks to the development of advanced diagnostic, surgical, and radiation techniques. However, these new technologies have come with numerous treatment-related side effects, including nausea, vomiting, pain, and anorexia, which are often uncontrolled.

oncology.pencis.com/” target=”_blank”>Cannabis products have gained popularity over the last decade to manage these symptoms in children with cancer, but little is currently known about its safety, efficacy, and dosing in this patient population.

oncology.pencis.com/” target=”_blank”>“Pediatric oncologists are understandably reluctant to authorize cannabis because of a lack of evidence supporting the safety and efficacy of its use in children with cancer,” the authors of the study wrote.1 “There is a strong need to map the evidence on the current use of cannabinoids in children with cancer to inform the development of clinical trials evaluating the safety, dosing, and efficacy of various cannabis products in children with cancer.”

oncology.pencis.com/” target=”_blank”>Investigators from the University of Manitoba conducted a systematic review and meta-analysis to assess the literature on the use of medical cannabis for symptom management in children with cancer. Data was gathered from 4 different databases: MEDLINE, Embase, PsycINFO, and the Cochrane Library.

oncology.pencis.com/” target=”_blank”>A total of 34611 total citations were identified based on types of cannabis products, doses, formulations, frequencies, routes of administration, indications, clinical and demographic details, reported efficacy outcomes, and adverse events. Of those, 19 studies consisting of 1927 participants were included in the study.

oncology.pencis.com/” target=”_blank”>Investigators found that the studies reported various cannabis products for the management of different symptoms, the most common of which was Award-call-for-profile/”>Chemotherapy-induced nausea and vomiting. Adverse events associated with the use of cannabis products included somnolence, dizziness, and dry mouth.

oncology.pencis.com/” target=”_blank”>Additionally, there were no serious adverse events related to the use of cannabis for the management of cancer-related symptoms in children across all of the studies that were included.

oncology.pencis.com/” target=”_blank”>“It was difficult to measure benefit across studies, given a range of different outcomes and study designs; however, in interventional studies with active control groups, cannabinoids performed better in managing nausea and vomiting,” Lauren E. Kelly, PhD, lead author on the study, said in a release.2 “Data are lacking on cannabinoids’ effects on pain, mood, sleep, and health-related quality of life.”

oncology.pencis.com/” target=”_blank”>Study limitations include number of studies included in the review, lack of uniformity in the outcomes of the included studies, inability to conduct quantitative synthesis of outcome data due to a high variability in reporting of data, and no included case-controlled or cohort studies in the review.

oncology.pencis.com/” target=”_blank”>“Given that some children report benefits and some children experience adverse events, it is critical that more rigorous studies evaluating the effects of cannabinoids on children with cancer are conducted and shared with parents, patients, and the health care community,” Kelly said.

oncology.pencis.com/” target=”_blank”>References
oncology.pencis.com/” target=”_blank”>1. Chhabra, M, Ben-Eltriki, M, Paul, A, et al. Cannabinoids for symptom management in children with cancer: a systematic review and meta-analysis. cancer. 2023; 1-15. doi:10.1002/cncr.34920
oncology.pencis.com/” target=”_blank”>2. Are cannabis products safe and effective for reducing symptoms in children with cancer? News Release. University of Manitoba. August 28, 2023. Accessed August 28, 2023. https://News.umanitoba.ca/are-cannabis-products-safe-and-effective-for-reducing-symptoms-in-children-with-cancer/

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oncology.pencis.com/”>oncology.pencis.com/”>

oncology.pencis.com/”>Prostate cancer is a leading cause of death among American men, and it’s resistant to one of the most powerful Award-call-for-profile/”>Chemotherapy medications — cisplatin. Now, researchers reporting in ACS Central Science have developed the first therapy of its kind that disrupts prostate cancer cells’ metabolism and releases cisplatin into the weakened cells, causing them to die. In mouse models, an orally administered version shrunk tumors substantially.

oncology.pencis.com/”>Cisplatin attacks testicular, breast, bladder, lung and ovarian cancer cells, damages their DNA and effectively destroys tumors. However, it’s not effective against prostate cancer for reasons that are unclear to scientists, and many advanced cases of the disease don’t respond to other therapies, such as Award-registration/”>Androgen deprivation. Previously, researchers have shown in mouse models that as the disease advances, tumor cells shift from glycolysis toward fatty acid oxidation to support their growth and division. So, Shanta Dhar and colleagues from Sylvester Comprehensive cancer Center at the University of Miami wanted to develop a therapy that would inhibit fatty acid oxidation in cancer cells by targeting a mitochondrial protein that is vital to the metabolic process, making the cells susceptible to cisplatin.

oncology.pencis.com/”>The researchers verified that human prostate cancer cells thrive using fatty acid oxidation by assessing the biopsies of 38 people with the disease. Then they screened several cisplatin-containing prodrug compounds, which release the platinum-based molecule when they’re broken down, to see if they could inhibit fatty acid oxidation. The cisplatin prodrug Platin-L, which has a cisplatin molecule bound to a 12-carbon fatty acid on one side and succinate on the other side, had the greatest effect by binding to a key protein required for long chain fatty acid transport, a primary step in this metabolic process. And in trials, Platin-L reduced the growth of prostate cancer cells by over 50% in several different cell lines.

oncology.pencis.com/”>To develop a treatment that could be taken orally, the researchers encapsulated Platin-L in nanoparticles made with a biocompatible polymer that targeted prostate cancer cells. They administered the nanoparticles to mouse models with cisplatin-resistant prostate cancer and observed that the tumors shrunk, whereas tumors in animals treated with saline or cisplatin grew. Additionally, the Platin-L Nanoparticle-treated mice had steady body weight, increased survival rates and didn’t display peripheral neuropathy. Because the treatment affects fatty acid metabolism, which can be elevated in other types of cancers, the researchers say their type of additive Platin-L therapy may also be applicable to additional aggressive and Award-call-for-profile/”>Chemotherapy-resistant cancers.

oncology.pencis.com/”>Reference: Kalathil AA, Guin S, Ashokan A, et al. New pathway for cisplatin prodrug to utilize metabolic substrate preference to overcome cancer intrinsic resistance. ACS Cent Sci. 2023. doi: 10.1021/acscentsci.3c00286

#OncologyConference #CancerResearch #OncologyAwards #CancerTreatment #OncologyCommunity #CancerCare #OncologyEducation #CancerSurvivorship #OncologyInnovation #CancerAwareness #OncologyLeadership #CancerPrevention #OncologyExcellence #CancerBreakthroughs #OncologyCollaboration #CancerAdvancements #OncologyImpact #CancerPatientsFirst #OncologyFuture #OncologyInspiration #CancerFighters #OncologyHeroes #CancerAwarenessMonth #OncologyProgress #CancerSolutions #OncologyExperts #CancerSurvivors #shorts #shortsvideo #cancerConference #OncologyConference #pencis #oncologyconference #CardioOnc #radonc #medonc #caxtx #GeriOnc #psyonc #oncorn #hsronc #camets #cancer #fuckcancer #cancersucks #breastcancerawareness #breastcancer #cancermemes #cancerousmemes #cancersurvivor #cancerawareness #cancerdemama #breastcancerawarenessmonth #cancerresearch #fightcancer #childhoodcancerawareness #beatcancer #childhoodcancer #cancerseason #breastcancersurvivor #cancerfree #cancerfighter #cancerous #fcancer #cancerwarrior #teamcancer #ovariancancer #americancancersociety #standuptocancer #cancerresearchuk #cancersupport #skincancer #cancermeme #cancer #feminismiscancer #curecancer #anticancer #cancerzodiac #prostatecancer #cancers #fucancer #pediatriccancer #cancerawareness #beatcancer #cancersucks #cancerresearch #cancerfighter #cancerwarrior #cancertreatment #cancersurvivor #cancerprevention #cancerawarenessmonth #cancerpatientsupport #breastcancer #prostatecancer #lungcancer #coloncancer #ovariancancer #pancreaticcancer #leukemia #Conference-registration-usd/”>Lymphoma #melanoma #braincancer #childhoodcancer #cancerfree #oncology #cancercare #cancerdiagnosis #cancerribbon #cancerjourney

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oncology.pencis.com/” target=”_blank”>Researchers are set to to combine expertise in drug discovery, artificial intelligence (AI), and experimental cancer models and platforms in a new programme to design the precision cancer drugs of the future.

oncology.pencis.com/” target=”_blank”>Under an academic and commercial collaboration between The Institute of cancer Research, London, the Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, and the company Vivan Therapeutics, a multi-disciplinary team will seek to create drugs that can counteract drug resistance.

oncology.pencis.com/” target=”_blank”>Drug resistance – where cancer adapts, evolves and becomes resistant to treatment – is one of the biggest challenges in cancer Research. Although a drug targeted at a specific weakness in a person’s cancer may initially be effective at stopping cancer growth, their tumour may develop resistance over time.

oncology.pencis.com/” target=”_blank”>The team will have a particular focus on creating drugs that could target KRAS, a notorious cancer-driving protein. Few currently approved drugs target KRAS, and patients usually become resistant within months to those that are available.

oncology.pencis.com/” target=”_blank”>Scientists at The Institute of cancer Research (ICR) led by Professor Paul Workman, a world leader in the discovery of small-molecule cancer drugs, and Dr Albert Antolin at IDIBELL, who is developing new strategies based on Big Data and AI to power drug design, will work with Vivan Therapeutics to create new, more effective targeted cancer drugs that could be less prone to the problem of resistance.

oncology.pencis.com/” target=”_blank”>The Research team aims to design and develop small molecules that could simultaneously target multiple weaknesses in cancers with faults in KRAS.

oncology.pencis.com/” target=”_blank”>Vivan Therapeutics has developed a collection of fruit fly models that have faults in KRAS, either alone or in combination with other gene faults that drive cancer growth. The company has also developed a technology platform to enable testing of cancer therapies at a high-throughput level.

oncology.pencis.com/” target=”_blank”>Dr Antolin will use sophisticated new computational methods to identify promising compounds that could target both KRAS and other cancer-driving proteins.

oncology.pencis.com/” target=”_blank”>Professor Workman will bring his extensive experience in drug discovery, and potentially test small molecules discovered in this project on cancer cells in his laboratory before testing the most promising compounds in fly models developed by Vivan.

oncology.pencis.com/” target=”_blank”>The team’s ultimate goal is to find compounds that can effectively slow the growth of cancer in selected fly models, which could then progress onto the next stage of drug discovery and development.

oncology.pencis.com/” target=”_blank”>Professor Paul Workman, Group Leader of the Signal Transduction and Molecular Pharmacology Team at the ICR, said:

oncology.pencis.com/” target=”_blank”>“I’m very much looking forward to working with the teams at IDIBELL and Vivan. Our goal is to find safe and effective new drugs that are less likely to evoke resistance than current drugs, by targeting multiple weaknesses in cancer at once – and that ultimately benefit cancer patients by giving them new treatment options that last longer than those that are currently available.”

oncology.pencis.com/” target=”_blank”>Dr Albert Antolin, principal investigator at IDIBELL, said:

oncology.pencis.com/” target=”_blank”>“I am really excited about this multi-disciplinary, industry-academia collaboration because the partners bring in very different and complementary expertise to tackle an important challenge that could make a big difference to many patients with cancers that harbour KRAS mutations.”

oncology.pencis.com/” target=”_blank”>Laura Towart, CEO of Vivan Therapeutics said:

oncology.pencis.com/” target=”_blank”>“We are thrilled to work with the Antolin and Workman labs to pioneer new therapies for hard to treat cancers. We utilise our in vivo high throughput drug screening platform to identify combinations of approved drugs to personalise patient treatment today but we are also committed to developing therapies of the future.”

#OncologyConference #CancerResearch #OncologyAwards #CancerTreatment #OncologyCommunity #CancerCare #OncologyEducation #CancerSurvivorship #OncologyInnovation #CancerAwareness #OncologyLeadership #CancerPrevention #OncologyExcellence #CancerBreakthroughs #OncologyCollaboration #CancerAdvancements #OncologyImpact #CancerPatientsFirst #OncologyFuture #OncologyInspiration #CancerFighters #OncologyHeroes #CancerAwarenessMonth  #OncologyProgress #CancerSolutions #OncologyExperts #CancerSurvivors  #shorts #shortsvideo #cancerConference #OncologyConference #pencis #oncologyconference  #CardioOnc  #radonc #medonc #caxtx #GeriOnc #psyonc #oncorn #hsronc #camets #cancer #fuckcancer #cancersucks #breastcancerawareness #breastcancer #cancermemes #cancerousmemes #cancersurvivor #cancerawareness #cancerdemama #breastcancerawarenessmonth #cancerresearch #fightcancer #childhoodcancerawareness #beatcancer #childhoodcancer #cancerseason #breastcancersurvivor #cancerfree #cancerfighter #cancerous #fcancer #cancerwarrior #teamcancer #ovariancancer #americancancersociety #standuptocancer #cancerresearchuk #cancersupport #skincancer #cancermeme #cancer #feminismiscancer #curecancer #anticancer #cancerzodiac #prostatecancer #cancers #fucancer #pediatriccancer  #cancerawareness #beatcancer #cancersucks #cancerresearch #cancerfighter #cancerwarrior #cancertreatment #cancersurvivor #cancerprevention #cancerawarenessmonth #cancerpatientsupport #breastcancer #prostatecancer #lungcancer #coloncancer #ovariancancer #pancreaticcancer #leukemia #Conference-registration-usd/”>Lymphoma #melanoma #braincancer #childhoodcancer #cancerfree #oncology #cancercare #cancerdiagnosis #cancerribbon #cancerjourney

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oncology.pencis.com/” target=”_blank”> In a recent study published in the journal of Genes & Diseases, Research team led by Lu explores the potential for the use of FDA-approved hypertension and EMA-approved cough medicines to revolutionize cancer treatment.

oncology.pencis.com/” target=”_blank”>cancer continues to be a pressing global health challenge, with pancreatic ductal adenocarcinoma (PDAC), colorectal cancer (CRC), and breast cancer (BC) ranking among the most prevalent and deadly. As the need for more effective, safe, and economical cancer treatment options intensifies, a team of scientists has discovered a promising breakthrough in the form of existing U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA)-approved drugs.

oncology.pencis.com/” target=”_blank”>Protein arginine methyltransferase 5 (PRMT5) overexpression has been linked to promoting the tumor phenotype in several cancers. Using an innovative AlphaLISA-based high-throughput screening method, the Research team identified Candesartan cilexetil (Can), an FDA-approved hypertension drug, and Cloperastine hydrochloride (Clo), an EMA-approved cough suppressant, as possessing notable PRMT5-inhibitory activity. Remarkably, the researchers validated the anti-tumor properties of these drugs using cancer phenotypic assays in vitro, confirming the reduction of both NF-κB methylation and its subsequent activation upon drug treatment.

oncology.pencis.com/” target=”_blank”>These findings provide compelling grounds for considering Can and Clo as anti-PRMT5 cancer therapies. The potential safe and rapid repurposing of these previously unknown PRMT5 inhibitors into clinical practice could save significant resources, streamline processes, and ultimately expedite the delivery of much-needed treatments to cancer patients.

oncology.pencis.com/” target=”_blank”>The concept of drug repurposing, particularly for drugs approved by the FDA or EMA, is not new. It has been widely adopted in drug discovery and development, delivering several success stories, such as Sildenafil (Viagra®), initially developed for hypertension and later repurposed to treat erectile dysfunction. The appeal lies in the established safety, efficacy, formulation, and toxicity profiles of such drugs. Repurposed drugs can reach approval up to 3-12 years faster and at approximately 50% lower cost compared to novel drugs. The current Research targets PDAC, CRC, and BC, responsible for a significant number of cancer-related deaths. Despite available Award-call-for-profile/”>Chemotherapy and targeted therapies, mortality rates continue to rise, and the costs associated with developing new treatments and patient care are astronomically high. This necessitates fast-paced, cost-effective solutions such as the repurposing of FDA-approved drugs.

oncology.pencis.com/” target=”_blank”>Detailed in the study, Can and Clo were found to significantly reduce cancer cell proliferation and tumor growth. The researchers employed in silico prediction methods to identify critical residues on PRMT5 targeted by these drugs, potentially interfering with its enzymatic activity. Consequently, these drugs exhibited marked reduction in tumor growth in vivo. Moving forward, the team is optimistic about exploiting PRMT5 as a therapeutic target for these cancers. This breakthrough in the cancer treatment landscape paves the way for future Research and applications, particularly in accelerating the repurposing of FDA-approved drugs and, in turn, the clinical treatment of some of the deadliest cancers.

oncology.pencis.com/” target=”_blank”>The study reinforces the critical role of drug repurposing in streamlining the lengthy and costly Drug Development process. It further underscores the potential of repurposed drugs in uncovering novel treatment targets, potentially transforming the cancer treatment landscape and providing an effective, safe, and economical solution for cancer patients. Despite these promising findings, further Research is required to explore the full potential of these market drugs as cancer therapies. The team remains dedicated to the pursuit of innovative solutions in the battle against cancer and hopeful for the future of cancer treatment.

oncology.pencis.com/” target=”_blank”>Source:

oncology.pencis.com/” target=”_blank”>TranSpread

oncology.pencis.com/” target=”_blank”>Journal reference:

oncology.pencis.com/” target=”_blank”>DOI: https://doi.org/10.1016/j.gendis.2022.04.001

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