Latest news with #NatureImmunology
Sydney Morning Herald
25-07-2025
- Science
- Sydney Morning Herald
The cancer drug, the faked data and the superstar scientist
On camera, Smyth looks nervous and drawn – a scientist out of water. But in recorded lectures to scientific colleagues, he looks far more assured. Dressed in black with his gelled grey hair, answering technical questions off the cuff, he is a man in command. 'He was a little bit aloof, he had a high opinion of himself. He saw himself as an upper-level person. But he was a nice-enough fellow,' said Brett*, a former colleague who spent time with Smyth outside work and, like others, requested anonymity to avoid professional repercussions. 'His arrogance comes across very quickly,' said a second. 'He had an ab-fab reputation,' said a third, who would later be charged with investigating him. 'That, more than anything else, is the biggest puzzle of all to me. He was not trying to achieve that level of reputation – he'd already achieved it. Why did he feel it was necessary to try for even higher acclaim than he'd already got?' From the outside, Smyth was a rising star, winning awards, publishing important papers, and being showered in millions of dollars of taxpayer research funding. But inside his lab, from the earliest days of his career, concerns were emerging. Selena*, who worked closely alongside Smyth during his time at Peter MacCallum Cancer Centre, said he only ever wanted to know the good news – even though science is littered with negative results. He 'did not want to hear about things that weren't working. He wanted to see finished results. He did not want to know how it was being done,' she said. 'You'd present raw data, and he'd say, 'You can just leave those points out – they are outliers'.' Other scientists sometimes could not reproduce his results. But rather than question Smyth, they often questioned themselves. 'Maybe he's got better hands than I have. Or maybe the mice are different,' said Brett*. 'There are all these variables.' In 2004, Smyth was the senior author on a paper in top journal Nature Immunology, which was such a sensation that his co-author was nominated for a National Association of Research Fellows award, where Professor David Vaux was secretary. Vaux, 65, is one of Australia's most important cancer researchers, past deputy director of the Walter and Eliza Hall Institute and winner of as many prizes as Smyth. He is also one of the very few researchers willing to take on the scientific establishment when he believes someone is committing research misconduct. A third thing to know about Vaux: when he goes to the doctor, he loves to read the Australian Women's Weekly. The puzzles where you have to spot differences between two images are his favourite. Vaux had first come across Smyth in 1995 when he was asked to comment on a paper the young researcher submitted. He came across paragraphs that seemed similar to Vaux's own work. But when the paper was published, those paragraphs had disappeared. Still, Vaux kept half an eye on the rising star. Years later, he found himself flicking through a 2004 paper Smyth had co-authored. It contained rows of flow cytometry plots of immune cells. Each dot is meant to represent a cell. 'I just looked at them, fused the images, and it was immediately clear they had been duplicated and altered,' said Vaux. The dot pattern kept repeating, as though someone had cut and pasted together the same images in a different order. Each plot contains 10,000 cells. 'The chances of two plots having the same pattern of dots would be 1 in 10 to the power of 1000.' Vaux emailed the paper's authors. 'I can clearly see the problems – one dotplot has been duplicated and modified and used for at least 6 of the plots presented in that revised figure. I still haven't been able to track Mark down,' one wrote back. 'I feel sick.' Nature Immunology launched an investigation and in 2006 retracted the paper because 'it contains a number of errors, including duplications of some flow cytometry plots'. To this day, it is not clear if it was Smyth who duplicated the plots. But a retraction is an enormous black mark on a scientist's career. Peter MacCallum Cancer Centre put in place compulsory research integrity training, including a seminar entitled 'Scientists Behaving Badly: Fraud & Misconduct'. This was only the start of Smyth's troubles. In 2014, a thin unmarked envelope was slipped under David Vaux's office door. Inside, under a cover note from 'a concerned scientist', was a copy of a secret Peter Mac investigation into Mark Smyth. The investigation started in 2012, when one of Smyth's PhD students was running a cancer experiment in mice. But the data wasn't good. It looked like another negative experiment. Then, according to the student's evidence, Smyth provided him with a new spreadsheet. It contained records of 20 mice Smyth claimed he had kept as a 'side project'. Smyth said he'd been running the same experiment – with better results. He suggested combining the data, making the results much more positive. At Peter Mac, mice were tracked closely on its Mighty Mouse database, which recorded their births, deaths and every experiment. The student could find no record of Smyth's additional mice on Mighty Mouse. He told Smyth, who suddenly advised tossing the new data. Instead, the concerned student went to Peter Mac, which launched a preliminary investigation. Smyth's personal lab book contained 'not entirely convincing' partial records for 14 of the mice, 'crowded into unlikely spaces', the preliminary investigative report, also obtained by this masthead, says. A further six mice were recorded in a book belonging to a lab assistant. But she told the inquiry she had no memory of monitoring the mice or writing the data in her lab book. She said the handwriting was not hers. 'The animal technicians are right on the ball. If they say a cage of mice, that they know Mark is talking about, never existed – it's not really possible,' one investigator told this masthead, speaking under condition of anonymity to detail confidential information. Peter Mac's preliminary investigation found no independent evidence the mice ever existed and concluded Smyth had a case to answer. 'I thought it wasn't marginal,' said the investigator. 'I thought at the time: 'This guy is in serious trouble here'.' But under an unusual arrangement, the University of Melbourne is responsible for conducting research misconduct investigations at Peter Mac. The sandstone institution would conduct the full investigation. A finding he had made up mice could end Smyth's glittering career. But Smyth's luck turned. On the day of his hearing in front of an expert panel, a Peter Mac employee produced a new datasheet. It was apparently written by Smyth and then 'mislaid'. The employee said they found it while clearing out his office. It contained an error-riddled record for the 20 mice. A handwriting expert brought in by the inquiry determined both this rediscovered loose sheet of paper and the records in the lab assistant's lab book – the ones she said she did not write – were likely written by the same person. That person may have been Smyth, the panel was told. But the expert couldn't be sure. Smyth claimed the central database that recorded mice was often faulty and not fit for purpose. Two of Smyth's colleagues told the panel they had similar problems with the database. One of those colleagues was the person who found Smyth's 'mislaid' data sheet. The other, Robert*, now says the panel misconstrued his evidence. 'When they asked me directly if the mice in question could have existed, I was very clear and responded with a 'no',' he said. 'It does haunt me that my statements have been twisted to allow Mark to escape punishment.' The panel concluded Smyth did not make up the data. He was in the clear. 'It's very hard to understand how Melbourne University could say he wasn't fabricating the data, making it up, and then six or seven years later he's done exactly the same thing at QIMR,' Robert told this masthead. 'Melbourne University needs to take some accountability for allowing Mark to continue misleading scientists and patients.' A senior Australian scientist with close knowledge of the case, speaking anonymously due to restrictions in their employment contract, is absolutely scathing. 'As they'd done with a number of integrity cases, [the University of Melbourne] … concluded there was nothing to see here,' they said. 'The institutional lens is: we have to avoid any suggestion the University of Melbourne has dodgy people, so let's find him not guilty and move him on.' University of Melbourne deputy vice chancellor Professor Mark Cassidy said in a statement that all complaints and allegations were taken seriously and addressed in line with the appropriate guidelines. GSK said its oncology research and development program was 'robust'. 'Our investigations of Nelistotug in combination with other therapies is always based on the full breadth of scientific evidence available,' it said. Smyth was hired by QIMR in 2012, before the Peter Mac allegations were made, and left to join the Queensland-based institute in 2013 - before the investigation was concluded. The allegations he faced soon became the subject of water-cooler gossip, both in Victoria and in Queensland. 'It was a pretty open secret at Peter Mac that Mark Smyth was fudging data,' said a former Peter Mac PhD student. 'No one believed it. It all looked fake.' Smyth himself has never spoken publicly about the saga, he left QIMR and this masthead was not able to confirm where he was now working. Approached recently at a house in a leafy Brisbane suburb a few minutes' drive from his former QIMR lab, he said he was 'not interested' in responding to the allegations, immediately turning down a printed list of questions as he unpacked golf clubs from his car. 'No thanks, I've been asked … a million times,' Smyth said. Asked twice if he stood by his work and research, he said: 'Can you please just get away. I'm not interested. See you later.'
The Age
25-07-2025
- Science
- The Age
The cancer drug, the faked data and the superstar scientist
On camera, Smyth looks nervous and drawn – a scientist out of water. But in recorded lectures to scientific colleagues, he looks far more assured. Dressed in black with his gelled grey hair, answering technical questions off the cuff, he is a man in command. 'He was a little bit aloof, he had a high opinion of himself. He saw himself as an upper-level person. But he was a nice-enough fellow,' said Brett*, a former colleague who spent time with Smyth outside work and, like others, requested anonymity to avoid professional repercussions. 'His arrogance comes across very quickly,' said a second. 'He had an ab-fab reputation,' said a third, who would later be charged with investigating him. 'That, more than anything else, is the biggest puzzle of all to me. He was not trying to achieve that level of reputation – he'd already achieved it. Why did he feel it was necessary to try for even higher acclaim than he'd already got?' From the outside, Smyth was a rising star, winning awards, publishing important papers, and being showered in millions of dollars of taxpayer research funding. But inside his lab, from the earliest days of his career, concerns were emerging. Selena*, who worked closely alongside Smyth during his time at Peter MacCallum Cancer Centre, said he only ever wanted to know the good news – even though science is littered with negative results. He 'did not want to hear about things that weren't working. He wanted to see finished results. He did not want to know how it was being done,' she said. 'You'd present raw data, and he'd say, 'You can just leave those points out – they are outliers'.' Other scientists sometimes could not reproduce his results. But rather than question Smyth, they often questioned themselves. 'Maybe he's got better hands than I have. Or maybe the mice are different,' said Brett*. 'There are all these variables.' In 2004, Smyth was the senior author on a paper in top journal Nature Immunology, which was such a sensation that his co-author was nominated for a National Association of Research Fellows award, where Professor David Vaux was secretary. Vaux, 65, is one of Australia's most important cancer researchers, past deputy director of the Walter and Eliza Hall Institute and winner of as many prizes as Smyth. He is also one of the very few researchers willing to take on the scientific establishment when he believes someone is committing research misconduct. A third thing to know about Vaux: when he goes to the doctor, he loves to read the Australian Women's Weekly. The puzzles where you have to spot differences between two images are his favourite. Vaux had first come across Smyth in 1995 when he was asked to comment on a paper the young researcher submitted. He came across paragraphs that seemed similar to Vaux's own work. But when the paper was published, those paragraphs had disappeared. Still, Vaux kept half an eye on the rising star. Years later, he found himself flicking through a 2004 paper Smyth had co-authored. It contained rows of flow cytometry plots of immune cells. Each dot is meant to represent a cell. 'I just looked at them, fused the images, and it was immediately clear they had been duplicated and altered,' said Vaux. The dot pattern kept repeating, as though someone had cut and pasted together the same images in a different order. Each plot contains 10,000 cells. 'The chances of two plots having the same pattern of dots would be 1 in 10 to the power of 1000.' Vaux emailed the paper's authors. 'I can clearly see the problems – one dotplot has been duplicated and modified and used for at least 6 of the plots presented in that revised figure. I still haven't been able to track Mark down,' one wrote back. 'I feel sick.' Nature Immunology launched an investigation and in 2006 retracted the paper because 'it contains a number of errors, including duplications of some flow cytometry plots'. To this day, it is not clear if it was Smyth who duplicated the plots. But a retraction is an enormous black mark on a scientist's career. Peter MacCallum Cancer Centre put in place compulsory research integrity training, including a seminar entitled 'Scientists Behaving Badly: Fraud & Misconduct'. This was only the start of Smyth's troubles. In 2014, a thin unmarked envelope was slipped under David Vaux's office door. Inside, under a cover note from 'a concerned scientist', was a copy of a secret Peter Mac investigation into Mark Smyth. The investigation started in 2012, when one of Smyth's PhD students was running a cancer experiment in mice. But the data wasn't good. It looked like another negative experiment. Then, according to the student's evidence, Smyth provided him with a new spreadsheet. It contained records of 20 mice Smyth claimed he had kept as a 'side project'. Smyth said he'd been running the same experiment – with better results. He suggested combining the data, making the results much more positive. At Peter Mac, mice were tracked closely on its Mighty Mouse database, which recorded their births, deaths and every experiment. The student could find no record of Smyth's additional mice on Mighty Mouse. He told Smyth, who suddenly advised tossing the new data. Instead, the concerned student went to Peter Mac, which launched a preliminary investigation. Smyth's personal lab book contained 'not entirely convincing' partial records for 14 of the mice, 'crowded into unlikely spaces', the preliminary investigative report, also obtained by this masthead, says. A further six mice were recorded in a book belonging to a lab assistant. But she told the inquiry she had no memory of monitoring the mice or writing the data in her lab book. She said the handwriting was not hers. 'The animal technicians are right on the ball. If they say a cage of mice, that they know Mark is talking about, never existed – it's not really possible,' one investigator told this masthead, speaking under condition of anonymity to detail confidential information. Peter Mac's preliminary investigation found no independent evidence the mice ever existed and concluded Smyth had a case to answer. 'I thought it wasn't marginal,' said the investigator. 'I thought at the time: 'This guy is in serious trouble here'.' But under an unusual arrangement, the University of Melbourne is responsible for conducting research misconduct investigations at Peter Mac. The sandstone institution would conduct the full investigation. A finding he had made up mice could end Smyth's glittering career. But Smyth's luck turned. On the day of his hearing in front of an expert panel, a Peter Mac employee produced a new datasheet. It was apparently written by Smyth and then 'mislaid'. The employee said they found it while clearing out his office. It contained an error-riddled record for the 20 mice. A handwriting expert brought in by the inquiry determined both this rediscovered loose sheet of paper and the records in the lab assistant's lab book – the ones she said she did not write – were likely written by the same person. That person may have been Smyth, the panel was told. But the expert couldn't be sure. Smyth claimed the central database that recorded mice was often faulty and not fit for purpose. Two of Smyth's colleagues told the panel they had similar problems with the database. One of those colleagues was the person who found Smyth's 'mislaid' data sheet. The other, Robert*, now says the panel misconstrued his evidence. 'When they asked me directly if the mice in question could have existed, I was very clear and responded with a 'no',' he said. 'It does haunt me that my statements have been twisted to allow Mark to escape punishment.' The panel concluded Smyth did not make up the data. He was in the clear. 'It's very hard to understand how Melbourne University could say he wasn't fabricating the data, making it up, and then six or seven years later he's done exactly the same thing at QIMR,' Robert told this masthead. 'Melbourne University needs to take some accountability for allowing Mark to continue misleading scientists and patients.' A senior Australian scientist with close knowledge of the case, speaking anonymously due to restrictions in their employment contract, is absolutely scathing. 'As they'd done with a number of integrity cases, [the University of Melbourne] … concluded there was nothing to see here,' they said. 'The institutional lens is: we have to avoid any suggestion the University of Melbourne has dodgy people, so let's find him not guilty and move him on.' University of Melbourne deputy vice chancellor Professor Mark Cassidy said in a statement that all complaints and allegations were taken seriously and addressed in line with the appropriate guidelines. GSK said its oncology research and development program was 'robust'. 'Our investigations of Nelistotug in combination with other therapies is always based on the full breadth of scientific evidence available,' it said. Smyth was hired by QIMR in 2012, before the Peter Mac allegations were made, and left to join the Queensland-based institute in 2013 - before the investigation was concluded. The allegations he faced soon became the subject of water-cooler gossip, both in Victoria and in Queensland. 'It was a pretty open secret at Peter Mac that Mark Smyth was fudging data,' said a former Peter Mac PhD student. 'No one believed it. It all looked fake.' Smyth himself has never spoken publicly about the saga, he left QIMR and this masthead was not able to confirm where he was now working. Approached recently at a house in a leafy Brisbane suburb a few minutes' drive from his former QIMR lab, he said he was 'not interested' in responding to the allegations, immediately turning down a printed list of questions as he unpacked golf clubs from his car. 'No thanks, I've been asked … a million times,' Smyth said. Asked twice if he stood by his work and research, he said: 'Can you please just get away. I'm not interested. See you later.'
Time Business News
24-07-2025
- Health
- Time Business News
Advancements in Genetically Engineered Models for Precision Research
A mice model refers to laboratory mice that are genetically engineers or breeds to study human diseases, drug reactions and biological processes. These models are widely used in biomedical research, due to their genetic similarity for humans, small reproductive cycles and ease of handling. The model of mice market growth is inspired by increasing demand for preclinical study, increase in drug discovery and investment in cancer research, progress in genetic engineering technologies such as CRISPR and increasing attention to individual medicine. Additionally, the requirement of accurate and cost-effective models for the study of complex diseases enhances the adoption of models of innovative and humanized mice. Key Growth Drivers and Opportunities Rising Demand for Preclinical Studies: The growing demand for preclinical studies is significantly increasing the growth of the market model of mice, as laboratory mice are essential tools in evaluating new drugs and remedies before human tests. Pharmaceutical and biotechnology companies greatly rely on the models of mice to stimulate human diseases, test drug candidates and assess biological reactions in a controlled environment. There is a growing requirement of models of exact, reliable and genetically engineer mice, especially in oncology, neurology and genetic disorders, with R&D investment. This bounce in pregnancy research accelerates the demand for models of advanced and human-to-human mice, fuel the expansion of the market and innovation. Challenges The mice models face many boundaries in the market that can obstruct its growth and effectiveness. A major challenge is a biological difference between mice and humans, which can lead to incorrect predictions of human reactions to drugs or diseases, limiting the translation value of research. Additionally, moral concerns about animal testing, with strict regulatory guidelines, can restrict the experiment and increase research costs. High maintenance and reproductive costs, especially for models of genetically modified or human rats, also create financial obstacles for small research institutes. In addition, increasing availability of optional in in vitro and computational models can reduce dependence on animal models over time. Innovation and Expansion Researchers Created the First Completely Working Human Immune System Mouse Model In July 2024, A biological research discovery offers fresh perspectives on disease modeling and immunotherapy development. Researchers at The University of Texas Health Science Center in San Antonio have developed a humanized mouse model that can mount certain antibody responses because it has a human immune system and a gut flora similar to that of humans. The multi-year effort, which was published in the August 2024 issue of Nature Immunology, aimed to build a humanized mouse with a fully functional human immune system in order to overcome the limits of the in vivo human models that are currently available. The resultant humanized mice, known as TruHuX (for truly human, or THX), have a complete and functional human immune system, complete with lymph nodes, germinal centers, human T and B lymphocytes, memory B lymphocytes, thymus human epithelial cells, and plasma cells that produce highly specific antibodies and autoantibodies that are exactly like those found in humans. The RenMice Series for Advanced Drug Discovery is Officially Launched by Biocytogen In September 2023, The RenMice series, which consists of a set of independently created, completely human antibody mice and TCR mice with exclusive intellectual property, was formally disclosed by Biocytogen Pharmaceuticals Co., Ltd. As 'human,' the term 'Ren' is derived from the Chinese pinyin for '人' (rén), which incorporates Eastern cultural elements and symbolizes Biocytogen's dedication to creating cutting-edge technologies that promote the discovery, development, and delivery of novel therapeutics, ultimately improving human health. RenMab, RenLite, RenNano, RenTCR, and RenTCR-mimic are the five strains of completely human antibody/TCR mice that make up the RenMice line. completely human monoclonal antibodies, bispecific antibodies, bispecific antibody-drug conjugates (BsADCs), nanobodies, completely human T-cell receptors (TCRs), and TCR-mimic antibodies have all been found using these animals. Inventive Sparks, Expanding Markets The key players operating in the mice model market include Charles River Laboratories, (US) The Jackson Laboratory (US), Taconic Biosciences, Inc. (US), Envigo (US), JANVIER LABS (France), genOway (France), PolyGene (Switzerland), Crown Biosciences (US), TransCure bioservices (France), Ingenious Targeting Laboratory (US), Cyagen Biosciences (US), GVK BIO (India), The Andersons, Inc. (US), Innovive (US), Allentown, LLC (US), FENGSHI Group (China), Ozgene Pty Ltd. (Australia), and Harbour Biomed (US). About Author: Prophecy is a specialized market research, analytics, marketing and business strategy, and solutions company that offer strategic and tactical support to clients for making well-informed business decisions and to identify and achieve high value opportunities in the target business area. Also, we help our client to address business challenges and provide best possible solutions to overcome them and transform their business. TIME BUSINESS NEWS
Time Business News
22-07-2025
- Health
- Time Business News
Breakthroughs in Humanized Mouse and Rat Model Technologies
Humanized mouse and rat models are laboratory rodents genetically engineers to carry human genes, cells, tissues, or immune systems, which enable researchers to study human-specific diseases, immune reactions, and effects of drugs in a living organism. The market is growing rapidly for these models due to rising demand for more predictive preclinical tools in oncology, infectious diseases and immunotherapy research. As traditional animal models often fail to mimic the accurate mimic of human biology, humanized rodents provided a more reliable platform for drug development, personal medical and translation research, which runs their adoption in drugs and educational fields. Key Growth Drivers and Opportunities Infectious Diseases and Immunotherapy Research: Increasing prevalence of infectious diseases and rapid expansion of immunotherapy research are the major driver of the humanized mouse and rat model market, as these models closely mimic human immune responses and disease progression. They provide an important platform to evaluate vacancies, antiviral drugs and immune-based treatments in human-affected context. With the increasing demand for individual and targeted remedies, especially in oncology and virology, the requirement of an exact pre -pricing model is rapidly growing, leading to indispensable equipment in translation and drug development research to human rodents. Challenges Humanized mouse and rat model market face high production costs, technical complexity in genetic engineering and limited enclosure efficiency of human cells or tissues in some models. Additionally, these rodents are not fully repeated to all aspects of human physiology, causing the disease progression and discrepancies in the reaction of the drug. Moral concerns and regulatory barriers also face challenges, especially in studies associated with human immune components or fetal tissue, potentially slow down widespread adoption and commercialization. Innovation and Expansion Researchers Create the First Whole Humanized Immune System in a Mouse Model In July 2024, Researchers at The University of Texas Health Science Center in San Antonio have developed a humanized mouse model that can mount certain antibody responses because it has a human immune system and a gut flora similar to that of humans. The multi-year effort, which was published in the August 2024 issue of Nature Immunology, aimed to build a humanized mouse with a fully functional human immune system in order to overcome the limits of the in vivo human models that are currently available. Human T and B lymphocytes, memory B lymphocytes, lymph nodes, germinal centers, thymus human epithelial cells, and plasma cells that produce highly specific antibodies and autoantibodies that are identical to those of humans are all present in the resulting humanized mice, known as TruHuX. Biologics UK Presents GemPharmatech's Humanized Mouse Models for COVID-19 and Bispecific Antibody Research In September 2021, At the Biologics UK Oxford Global Conference, held September 6–8, 2021, in London, UK, GemPharmatech co-hosted a panel discussion on bispecific antibodies and showcased its humanized mouse models to promote T-Cell Bispecific antibody and COVID-19 preclinic development. Hundreds of academic and industry researchers, as well as commercial partners from across the world, attended the conference, which is the largest in-person biologics event in London. Large pharmaceutical and biotech companies, contract research organizations (CROs), universities, and research institutions across the US are among the R&D communities that GPT serves with animal models and related services. GPT has partnered with these organizations in the US to enable shorter shipping times and lower costs. Inventive Sparks, Expanding Markets The key players operating the humanized mouse and rat model market involves Vitalstar Biotechnology, The Jackson Laboratory, Taconic Biosciences, Ingenious Targeting Laboratory, Horizon Discovery (Sage Labs), Hera Biolabs, Genoway, Crown Bioscience (Subsidiary Of Jsr Corporation), Champions Oncology, And Axeni. Prominent players operating in the target market are focusing on strategic partnerships as well as the launching of the products to gain a competitive edge in the target market. About Author: Prophecy is a specialized market research, analytics, marketing and business strategy, and solutions company that offer strategic and tactical support to clients for making well-informed business decisions and to identify and achieve high value opportunities in the target business area. Also, we help our client to address business challenges and provide best possible solutions to overcome them and transform their business. TIME BUSINESS NEWS
Medscape
16-07-2025
- Health
- Medscape
Circadian Disruption: The Hidden Cancer Link?
Circadian rhythms regulate the sleep-wake cycle, hormone secretion, metabolism, immune responses, and even patterns of eating and digestion. They help preserve genomic stability, control the cell cycle, and support tissue-level immunity. Disruptions to this internal clock, caused by sleep problems, nighttime light exposure, and irregular eating habits, are increasingly linked to the development of cancer. Researchers have observed altered clock gene expressions in the lung, breast, colorectal, leukemia, hepatocellular carcinoma, and glioblastoma tissues. The study, published in Nature Immunology, was led by Bridget M. Fortin, a doctoral candidate in biological chemistry at the University of California, Irvine, United States. She and her colleagues examined whether internal and external circadian disruptions, such as nighttime sleep loss, artificial light exposure, and irregular eating patterns, contributed to the early development of colorectal cancer (CRC). They also examined whether chrono medicine could help optimize chemotherapy and immune checkpoint inhibitor therapy. Numerous studies have linked circadian disruption to both cancer initiation and progression. Tumor samples frequently show reduced expression of core clock genes, and mutations in these genes are associated with poor survival rates. In CRC, lower levels of BMAL1, CRY1, CRY2, and PER1-PER3 are associated with reduced overall survival. Cancer Risk Since the mid-1970s, the overall cancer incidence has increased, particularly among individuals aged 15-39 years, with an early onset CRC showing the sharpest rise. Over the same period, exposure to artificial light at night (ALAN) has significantly increased. Light emitted from TVs, computer screens, and smartphones can suppress melatonin production, disrupting both sleep and circadian rhythms. A recent meta-analysis involving more than 170,000 participants found that high ALAN exposure increased the risk for estrogen receptor-positive breast cancer in premenopausal women. Similar associations have been reported for thyroid cancer. Crossing time zones may also disrupt circadian rhythms and potentially influence cancer risk. The gastrointestinal tract is particularly sensitive to circadian disruption. The intestinal mucosa regenerates on a precise 24-hour cycle, and the gut microbiome is highly responsive to rhythm disruption. Dietary intake is also regulated by the circadian clock, and dysregulation may emerge as a significant risk factor for CRC, although further confirmation is needed. Preserving circadian rhythms may play a significant role in the prevention and treatment of cancer in the future. Strategies include maintaining consistent sleep and mealtimes, limiting night-shift work, and limiting food intake to a 6- to 12-hour window during the day. Regular physical activity may have a positive effect on circadian rhythms. Chronotherapy involves the administration of cancer therapies that align with the body's internal clock. This can improve drug tolerability and potentially boost treatment efficacy. However, whether this contributes to treatment effectiveness remains uncertain. Similarly, the timing of administration could also play a key role in immunotherapy with checkpoint inhibitors with circadian rhythms, which may improve immunotherapy outcomes; however, this requires confirmation through further studies.
