All organisms have thioredoxin reductase (TR) or glutathione reductase (GR), the only enzymes that use reduced nicotinamide adenine dinucleotide phosphate to reduce cytosolic disulfides into thiols, thereby powering deoxyribonucleotide biosynthesis, elimination of oxidants, oxidative damage repair and reduction of the disulfide nutrient cystine into the thiol amino acid cysteine. Hence, TR/GR-null bacteria or yeast are inviable; yet, remarkably, mice with TR/GR-null livers thrive, in part by synthesizing life-sustaining cysteine through alternative pathways that evolved in metazoans. Although TR/GR-null livers generate some of their cysteine through the serine transsulfuration pathway, we here show that most cysteine in TR/GR-null livers comes from a pathway in which pyridoxal-phosphate-dependent cleavage of a carbon-sulfur bond in cystine generates cysteine persulfide, which decomposes nonenzymatically into cysteine. This potent yet previously unrecognized pathway is regulated by cellular levels of sulfur metabolites and represents a potent cytoprotective response that might be induced in most mammalian cells under conditions that chronically elevate cytosolic cystine levels.

Reactive sulfur species (RSS) are increasingly recognized as important bioactive agents across phyla. Application of newly developed chemical tools, detection methods and multi-omics techniques has uncovered new and specific roles of endogenous RSS and revealed that a number of biological actions previously attributed to reactive oxygen species or reactive nitrogen species can also be mediated by RSS. This Review describes the versatile chemical biology of RSS with focus on persulfide formation on cysteine residues. We examine their pro-oxidant and antioxidant capacities, involvement in redox signaling and metabolic pathways, stress responses, and their role in the pathophysiology of major disease groups, including cardiovascular and neurodegenerative diseases and cancer. We also provide a critical discussion of available detection methods and potential pharmacological and genetic approaches to adjusting persulfide levels. We cover current knowledge and its limitations, along with practical recommendations for advancing persulfide-based therapeutic interventions.

Lamin A/C proteins, integral to the nuclear lamina and present throughout the nucleoplasm, contribute to the mechanical stability of the nucleus and influence transcription as seen in laminopathies like certain lipodystrophies and progeria. By using light-sheet fluorescence correlation spectroscopy (FCS), earlier, we proved that lamin A is an important determinant of chromatin viscoelasticity in murine adult fibroblasts (MAFs). Here, by using MAF wild-type and lamin A knockout (KO) cells, we aimed to clarify the role of lamin A in chromatin organization and the DNA binding of PPARγ, a key transcription factor in adipogenesis also implicated in lipodystrophies. We analyzed the distribution of chromatin marks by confocal microscopy and measured PPARγ mobility and DNA binding by FCS and fluorescence recovery after photobleaching (FRAP). Conspicuous overall changes were detected upon lamin A depletion and PPARγ agonist (rosiglitazone) treatment. Confocal imaging showed a remarkable decrease in nuclear volume in the absence of lamin A and an increase upon rosiglitazone treatment indicating chromatin decondensation. Heterochromatin was enriched in a distinct peripheral rim, and the thickness of the constitutive heterochromatin rim diminished in the absence of lamin A. Colocalization analysis showed that the overlap between euchromatin and heterochromatin decreased in lamin A KO cells. PPARγ colocalized with euchromatin, whereas its localization was anti-correlated with constitutive heterochromatin, especially in the absence of lamin A. FCS and FRAP indicated that PPARγ had a fast-diffusing fraction bound with short residence times on DNA and a slow, more stably bound fraction throughout the nucleus including the periphery. Rosiglitazone increased PPARγ's colocalization with the euchromatin and enhanced its DNA binding, which was more pronounced in lamin A KO cells. Our results suggest that lamin A plays a primary role in determining nuclear volume and overall chromatin organization with likely functional consequences exemplified by regulating ligand-induced DNA binding of PPARγ, which may have epigenomic and transcriptional consequences.

ACE2 binding of spike proteins and concomitant viral uptake are the first and most decisive membrane-coupled events of SARS-CoV-2 infection, which rely on cholesterol-rich lipid raft microdomains of the host cell plasma membrane. Therefore, lowering membrane cholesterol levels may combat the infection, potentially complementing specific, resistance-prone antiviral approaches such as vaccines. High-throughput flow cytometry and quantitative 3-dimensional microscopy reveal that SH42, a novel, extremely potent, and highly selective 24-dehydrocholesterol reductase (DHCR24) blocker, markedly inhibits ACE2 binding of SARS-CoV-2 spike receptor-binding domains and entry of spike trimers of Wuhan-Hu-1 (WT), Delta, and Omicron BA.1 variants into living cells. These effects are related to SH42-induced reduction of plasma membrane cholesterol abundance and subsequent lipid raft disruption, which are accompanied by decreased cell surface ACE2 expression and its lowered raft partitioning. SH42 exhibits superior efficacy and potency in all aspects compared to the reference atorvastatin. Furthermore, inhibitory effects of SH42 are also corroborated by reduced SARS-CoV-2 RNA copy numbers of replication-competent complete virions of WT-resembling D614G, Delta, and Omicron-derived JN.1 strains. These results suggest that selective DHCR24 blockers such as SH42 may be promising novel candidates for inhibiting initial membrane-coupled events of SARS-CoV-2 infection and serve as potential alternative therapeutic option for COVID-19.

Constitutive activation of hypoxia-inducible factor 1 (HIF-1) in vhl-1(ok161) mutant Caenorhabditis elegans induces a characteristic phenotype marked by extended lifespan, reduced body size, and broad metabolic reprogramming. However, the underlying determinants mediating these adaptations remain incompletely understood. Here, we show that HIF-1 activation drives a distinct sulfur metabolic state characterized by the accumulation of hydrogen sulfide (H₂S) and persulfide species, accompanied by extensive remodeling of the mitochondrial proteome and altered stress sensitivity. Strikingly, these organismal and metabolic phenotypes require the mitochondrial sulfide:quinone oxidoreductase SQRD-1 (SQOR), which catalyzes the first step of sulfide oxidation. Loss of sqrd-1 abolishes the lifespan extension and small-body phenotype of vhl-1 mutants and reverses their proteomic, mitochondrial, and metabolic profiles toward wild-type levels. Mechanistically, SQRD-1-dependent sulfide oxidation establishes a redox state that shapes mitochondrial function, including suppression of respiratory capacity and modulation of oxidative stress responses. Consistent with this, quantitative proteomics revealed coordinated regulation of mitochondrial pathways and sulfur oxidation enzymes in vhl-1 mutants that is lost in vhl-1;sqrd-1 double mutants. Functional analyses identified mitochondrial complex I subunits (NUO-4 and NUO-5) as downstream effectors linking this metabolic state to lifespan and body-size regulation. Together, these findings identify SQRD-1 as a critical determinant of the metabolic and physiological outcomes of chronic HIF-1 activation, defining a sulfide-dependent redox state that couples hypoxia signaling to mitochondrial function and organismal adaptation. This work highlights mitochondrial sulfide oxidation as a key regulatory node in hypoxia responses and a potential target for modulating stress resistance and metabolic health.

Skeletal muscle dysfunction during spaceflight arises from combined mechanical and non-gravitational stressors. Here, we modeled solar particle event-like proton irradiation in C2C12 myogenic cells to examine radiation-induced membrane and mechanosensitive channel alterations. Proton exposure increased membrane rigidity in a dose-dependent manner and significantly reduced the pharmacological activatability of Piezo1 channels, identifying membrane-mediated mechanotransduction as a potential contributor to radiation-induced muscle dysfunction.

Molecular order-related bulk membrane properties that substantially modulate protein functions can be examined with environment-sensitive probes, such as the prototypical and most widely applied solvatochromic Laurdan, whose spectral parameters change depending on the local hydrophobicity. Di-4-ANEPPDHQ is a widely accepted Laurdan alternative with more favorable spectral properties suitable for standard imaging, and information provided by the two fluorophores is generally considered equivalent. In our study, using fluorescence-based experimental approaches, we demonstrate that different sterols distinctly alter di-4-ANEPPDHQ spectral properties, and these changes do not correlate with those observed with Laurdan. Our molecular dynamics simulations reveal that this may be caused by their distinct depth localization in bilayers since the sensor moiety of di-4-ANEPPDHQ is localized in the vicinity of the membrane-water interface as opposed to that of Laurdan lying near the hydrophobic core. Therefore, di-4-ANEPPDHQ can be considered as a complementary tool rather than an equivalent substitute of Laurdan.

The European Code Against Cancer (ECAC) provides evidence‐based public health recommendations to reduce cancer risk across Europe. First launched in 1987, it is periodically updated mainly to reflect scientific advances. The 5th edition (ECAC5), released for the medical oncology community in 2025 and to be presented to the public in 2026, aims to offer an authoritative and practical tool for cancer prevention for individuals and policymakers. Developed by over 60 experts across five Working Groups, ECAC5 expands the 12 recommendations of the 4th edition to 14, incorporating the latest evidence on modifiable cancer risks and effective medical interventions. Key innovations include new guidance on air pollution, cancer‐related infections, lung cancer screening and strengthened recommendations on tobacco, alcohol, diet, body weight, and occupational and radiation exposures. A major advancement is the addition of dedicated policy recommendations, acknowledging that many prevention measures require supportive environments and regulation. By aligning cancer prevention with broader noncommunicable disease strategies, ECAC5 aims to enhance uptake and impact. Its effective implementation could prevent up to 40% of new cancers in the EU.

Molecular-order-related membrane biophysical properties contribute to the functional modulation of transmembrane proteins, and therefore, their changes due to a modified membrane composition in diseases associated with alterations in lipid levels may play important pathophysiological roles. In living cells, membrane biophysics can be examined with environment-sensitive fluorophores that describe the structural organization of biological bilayers from different aspects. Microviscosity-sensitive probes such as TMA-DPH characterize the degree of motional freedom, that is, fluidity, polarity-sensitive dyes including Laurdan or PY3174 report on the extent of water penetration, that is, hydration, whereas voltage-sensitive fluorophores such as di-8-ANEPPS quantify the nonrandom alignment of molecular dipoles, that is, the dipole potential. Given that all of the above properties are intrinsically linked to the arrangement of membrane constituents, such parameters are assumed to change in parallel with each other, and thus, the information gained by the environment-sensitive fluorophores is generally considered equivalent. In the current study, using fluorescence-based measurement techniques and manipulating membrane sterol levels with cyclodextrin-based complexes in living cells, we experimentally demonstrate incongruent changes in fluorescence properties of TMA-DPH, Laurdan, PY3174, and di-8-ANEPPS. Comparative MD simulations reveal that this can be due to the distinct membrane localization of the fluorophores. Our experimental and computational analyses reveal that the most commonly applied environment-sensitive fluorophores depict the structural organization of membranes at different depths and suggest that a comprehensive investigation of bilayer structure should include an appropriate combination of dyes, which would be required for a better understanding of membrane biophysics and its potential roles in disease pathogenesis.

Abstract Background: Newly discovered malignancies at a relatively younger age (<50) are of great scientific interest. Previous studies found that the incidence of these early-onset cancers showed a global increase, although the pattern varied by cancer type. However, analysis of the Hungarian data has not yet been published. Methods: The Hungarian National Cancer Registry (HNCR) is responsible for data collection of the Hungarian cancer patients. Its operation is population-based in accordance with international standards and covers the entire country. Based on the 10th Revision of International Statistical Classification of Diseases and Related Health Problems, newly discovered cancer cases were extracted from the HNCR’s database. The query focused on patients between the ages of 20 and 49 and period from 2001 to 2019. Next to absolute case numbers, age-standardized values were also analyzed (reference: European Standard Population 2013). Spearman’s correlation test was performed to identify gender- and disease-specific trends. Results: During the studied period, the incidence of early-onset cancers showed decrease among males, while it did not change among females. It should be noted that compared to the total number of newly discovered cancer cases, the proportion of early-onset cancers showed decreasing trend in both genders. Categorization by cancer type revealed that among younger age the incidence of female breast and uterine corpus cancer elevated, while cervical cancer showed a decrease - the latter trend exceeded that of the general population. The incidence of colorectal cancer did not change among females, but decreased among males. The incidence of tobacco-related lung cancer and head and neck region decreased. Conclusion: Compared to analyses enrolled global trends, the Hungarian situation of early-onset cancers seemed to be more complex. On one hand, activities in the past few years such as introduction of HPV vaccination and restrictions on smoking resulted a decrease in the number of related cancers. On the other hand, new mechanisms underlying the increasing types of cancers (e.g. breast cancer) need to be identified. Citation Format: István Kenessey, András Wéber, Mária Dobozi, István Szatmári, Petra Parrag, Péter Nagy, Magdolna Dank, . Incidence of early-onset solid cancers in Hungary in the first two decades of the 21st century based on a population-based registry [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3569.

Despite the growing cancer burden in the European Union, public awareness of effective prevention is low. In response, Europe's Beating Cancer Plan has supported the development of the 5th edition of the European Code Against Cancer (ECAC5). Using a transparent, stepwise decision-making process, around 80 experts reviewed the latest scientific evidence on cancer prevention and used modern communication strategies to update the previous edition. An innovation in ECAC5 is the inclusion of population-level recommendations, aiming to structurally influence the systems that shape individual choices and improve environmental conditions to which all citizens are involuntarily exposed. ECAC5 includes 14 actionable, evidence-based recommendations for individuals to reduce their cancer risk alongside their respective policy recommendations. All are presented through equity lens, with attention to co-benefits for preventing other non-communicable diseases and tailoring messages to diverse audiences. Clear evidence-based statements on cancer risks factors and effective preventive interventions will empower citizens to make healthier choices, call policymakers to act, foster public support for effective policies, and contribute to more effective cancer prevention.

OBJECTIVES:Hungary is among the countries with the highest cancer mortality burden in Europe, consequently there is a crucial need to monitor changes in death rates in the population using appropriate surveillance tools. The Lexis diagram provides a means to depict age, period and cohort influences on long-term cancer mortality trends. METHODS:Age-specific mortality rates for six cancer localizations were constructed based on the Deaths Register of the Hungarian Central Statistical Office and the Human Mortality Database, then smoothed (p-splines) within the cells of the Lexis diagram assuming Poisson distribution. After calculating the annual percentage change in mortality rates, the results were visualized using heat maps. RESULTS:Substantial reduction in mortality was observable from the mid-1990s in both sexes as a strong period effect, depicting two distinct epidemiological eras in Hungary. Since 2010, breast cancer mortality in women among ages 70-90 (those born between 1930 and 1950) has been rising. Women born between 1940 and 50 experienced two plateaus in lung cancer mortality, unlike men, emphasizing the delayed nature of the smoking epidemic. CONCLUSIONS:The results align with cancer transition patterns observed in similarly developed countries and emphasize a critical need to expand the implementation of effective primary and secondary prevention measures. This includes sustaining organized screening and anti-smoking programs, as well as introducing lung cancer screening with low-dose CT.

The alpha-ketoglutarate dehydrogenase complex (KGDHc), also known as the 2-oxoglutarate dehydrogenase complex, plays a crucial role in oxidative metabolism. It catalyzes a key step in the tricarboxylic acid (TCA) cycle, producing NADH (primarily for oxidative phosphorylation) and succinyl-CoA (for substrate-level phosphorylation, among others). Additionally, KGDHc is also capable of generating reactive oxygen species, which contribute to mitochondrial oxidative stress. Hence, the KGDHc and its dysfunction are implicated in various pathological conditions, including selected neurodegenerative diseases. The pathological roles of KGDHc in these diseases are generally still obscure. The aim of this study was to assess whether the mitochondrial malfunctions observed in the dihydrolipoamide succinyltransferase (DLST) and dihydrolipoamide dehydrogenase (DLD) double-heterozygous knockout (DLST+/-DLD+/-, DKO) mice are associated with neuronal and/or metabolic abnormalities. In the DKO animals, the mitochondrial O2 consumption and ATP production rates both decreased in a substrate-specific manner. Reduced H2O2 production was also observed, either due to Complex I inhibition with α-ketoglutarate or reverse electron transfer with succinate, which is significant in ischaemia-reperfusion injury. Middle-aged DKO mice exhibited minor cognitive decline, associated with microgliosis in the cerebral cortex and neuronal death in the Cornu Ammonis subfield 1 (CA1) of the hippocampus, indicating neuroinflammation. This was supported by increased levels of dynamin-related protein 1 (Drp1) and reduced levels of mitofusin 2 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in DKO mice. Observations on activity, food and oxygen consumption, and blood amino acid and acylcarnitine profiles revealed no significant differences. However, middle-aged DKO animals showed decreased performance in the treadmill fatigue-endurance test as compared to wild-type animals, accompanied by subtle resting cardiac impairment, but not skeletal muscle fibrosis. In conclusion, DKO animals compensate well the double-heterozygous knockout condition at the whole-body level with no major phenotypic changes under resting physiological conditions. However, under high energy demand, middle-aged DKO mice exhibited reduced performance, suggesting a decline in metabolic compensation. Additionally, microgliosis, neuronal death, decreased mitochondrial biogenesis, and altered mitochondrial dynamics were observed in DKO animals, resulting in minor cognitive decline. This is the first study to highlight the in vivo changes of this combined genetic modification. It demonstrates that unlike single knockout rodents, double knockout mice exhibit phenotypical alterations that worsen under stress situations.

Background:Despite well-documented clinical differences across breast-cancer (BC) molecular subtypes and relevant changes in therapeutic interventions over the past decades, there remains a significant lack of up-to-date epidemiologic data and real-world outcomes, particularly in Central and Eastern Europe. Methods:This was a nationwide, retrospective study using the claims databases of the Hungarian National Health Insurance Fund (NHIF) that included patients who were newly diagnosed with BC between 2011 and 2020. BC subtypes were defined based on the therapies received. Overall survival (OS) and net survival rates were calculated. Results:Between 2011 and 2020, 74,143 patients were newly diagnosed with BC based on ICD-10 diagnostic codes in the NHIF database and 80.1% of the cases could be classified into subtypes based on therapy. The most common subtype was HER2-/HR+ BC, identified in 61.9% of patients, followed by triple negative breast cancer (TNBC) in 8.4%, HER2+/HR+ BC in 6.2%, and HER2+/HR- BC in 3.6% of cases. The proportions of TNBC and HER2+/HR+ were higher among younger patients, than in elderly cohorts. The 5-year OS of the total BC population was 74.2% in patients diagnosed between 2015-2019. Patients with TNBC had the poorest 5-year OS (TNBC: 61.4%; HER2+/HR+: 86.5%; HER2-/HR+: 79.1%; HER2+/HR-: 71.9%). Net survival rates (i.e. survival rates after adjusting the effects of other causes of death) varied across diagnostic periods and molecular subtypes. In most cases, patients diagnosed later during the study period tended to have numerically better survival rates. Patients with HER2-/HR+ BC had the most favorable net survival, with 5-year net survival exceeding 92% during the whole observation period, while TNBC patients had the lowest 5-year net survival rates ranging between 63.6% and 65.8% during the study period. Conclusion:Our nationwide study describes the distribution and survival of BC patients with different subtypes based on a retrospective analysis of the health insurance fund database. There remains a significant room for improvement in the survival of more aggressive molecular subtypes including HR-/HER2+ and triple-negative BC, which are more common in younger age cohorts.

Sulfite oxidase (SOX) deficiency is a rare inborn error of cysteine metabolism resulting in severe neurological damage. In patients, sulfite accumulates to toxic levels, causing a rise in the downstream products S-sulfocysteine, which mediates excitotoxicity, and thiosulfate, a catabolic intermediate/product of hydrogen sulfide (H2S) metabolism. Here, we report a full-body knockout mouse model for SOX deficiency (SOXD) with a severely impaired phenotype. Among the urinary biomarkers, thiosulfate showed a 45-fold accumulation in SOXD mice, representing the major excreted S-metabolite. Consistently, we found increased plasma H2S, which was derived from sulfite-induced release from persulfides, as demonstrated in vitro and in vivo. Mass spectrometry analysis of total protein persulfidome identified a major loss of S-persulfidation in 20% of the proteome, affecting enzymes in amino acids, fatty acid metabolism, and cytosolic iron-sulfur cluster biogenesis. Urinary amino acid profiles indicated metabolic rewiring and mitochondrial dysfunction, thus identifying an altered H2S metabolism and persulfidation in SOXD. Finally, oxidized glutathione and glutathione trisulfide were able to scavenge sulfite in vitro and in vivo, extending the lifespan of SOXD mice and providing a mechanistic concept of sulfite scavenging for the treatment of this severe metabolic disorder of cysteine catabolism.

The cancer problem is expanding, particularly in low‐ and middle‐income countries (LMICs). Preventive measures can reduce the incidence by 40–50%, and cure rates have increased during the past decades in a number of cancers. However, optimizing prevention programmes and increasing cure rates of cancer remain significant research challenges. The main focus of the conference was on P4 Cancer Medicine (Predictive, Preventive, Personalized and Participatory), a comprehensive strategy encompassing Health‐Related Quality of Life (HRQoL) research, aiming to enhance the well‐being of patients and individuals at risk. Addressing the cancer problem requires two key elements: translational cancer research and the development of relevant infrastructures. A Comprehensive Cancer Centre (CCC) acts as an innovation hub by integrating high‐quality, multidisciplinary therapy and care, with healthcare‐dependent prevention, research, and education. The United States has been at the forefront, providing quality‐assured CCCs and the Cancer Moonshot for strategic cancer research. The EU has followed with the European Research Council for basic research, the European Innovation Council to boost disruptive innovation, and two EU initiatives on cancer, Europe's Beating Cancer Plan (EBCP) and the Mission on Cancer. The increasing complexity of cancer biology and technologies presents both a research challenge and a healthcare demand. For most patients, a CCC is not available. A critical discussion focused on quality assurance of healthcare outside the catchment area of a CCC and involving patients in clinical research. The strategic deployment of resources to support collective healthcare efforts and research aimed at reducing the cancer problem was discussed with representatives from the United States, EU, Africa, China, India and Taiwan. Analyses of translational cancer research have revealed important gaps in implementing innovations, assessment of clinical effectiveness, HRQoL, outcome and health economics research. The increased release of new anticancer agents over the last 25 years, accompanied by insufficient information on clinical benefits, presents both an economic and ethical problem. Direct healthcare costs have increased due to expenses for anticancer agents for the treatment of patients with incurable diseases. Evidence‐based treatment based on HRQoL research is an unmet need. Basic/preclinical research aimed at increasing the cure rate should identify new, broader targets for therapy and develop extended diagnostic technologies for stratifying patients, to inform innovative clinical trials. Present research strategies convert cancer to a chronic disease, a growing burden for the healthcare systems. The increasing complexity of cancer biology and technology, the growing need for translational cancer research, and the demand for supporting infrastructures underscore the importance of international collaborations between CCCs. However, funding for cancer research is not currently aligned to reduce the cancer problem. While public funding for cancer research doubled between 2005 and 2024, the pharmaceutical industry's spending on cancer research increased tenfold. Increasing funding by public and non‐profit funding organizations is mandatory. Education is another significant need, but it is currently fragmented and underfunded. The last session of the conference summarized the strategies in a Statement with a strong emphasis on global collaboration addressing the growing cancer burden and pronounced inequalities. Expanding partnerships and fostering innovative, multidisciplinary approaches to cancer prevention, therapeutics/care, as well as research, are not just urgent but essential steps towards reducing incidence, increasing cure rates and enhancing the well‐being of cancer patients. Data‐driven cancer medicine is currently under development, and modern communication technologies for diagnostics may facilitate interactions across geographical distances. A global cancer research agenda can become a model of solidarity, sustainability, and ethical responsibility.

Background:The assessment of cancer survival is crucial for evaluating advancements in cancer management. As part of the nationwide HUN-CANCER EPI study, we examined the net survival of the Hungarian cancer patient population in 2011-2019. Methods:Using extracted data from the Hungarian National Health Insurance Fund (NHIF) database, the HUN-CANCER EPI study aimed to assess net survival probabilities for various cancer types over the past decade by the Pohar Perme Estimator method, providing insights for sex and age-specific differences and enabling comparative analysis with other European countries. Results:Between 2011 and 2019, 526,381 newly diagnosed cancer cases were identified, with colorectal, lung, breast, prostate, and bladder cancers being the most common. Age-standardized 5-year net survival rates showed significant improvements from 2011-12 till 2017-19 periods for colorectal cancer from 55.08% to 59.78% (4.70%), lung cancer from 20.10% to 23.55% (3.45%), liver cancer from 11.21% to 16.97% (5.76%) and melanoma from 90.06% to 93.80% (3.73%), while clinically relevant, but not significant improvements for breast cancer from 85.03% to 86.84% (1.81%), prostate cancer from 88.13% to 89.76% (1.63%) and thyroid cancer from 87.23% to 92.36% (5.12%). Women generally had better survival probabilities, with notable variations across cancer types. We found no significant age-related differences in cancer survival in women, while survival improvements of colorectal cancer were more pronounced in younger cohorts among male patients. International comparisons using different mortality life tables demonstrated favorable breast and prostate cancer survival rates in Hungary compared to other Central Eastern European countries. Conclusion:The HUN-CANCER EPI study revealed positive trends in cancer survival for most cancer types between 2011 and 2019. The study highlights the continued positive trajectory of cancer survival in Hungary like to more developed European countries.