Molecular Oncology最新文献

The 5th edition of the European Code Against Cancer (ECAC5) recommends sustainable, organised screening programmes for: (a) colorectal cancer using biennial quantitative faecal immunochemical test (FIT) for individuals aged 50-74 years. As an alternative strategy, once-only endoscopy may be considered within the same age range; (b) breast cancer using biennial digital mammography for women aged 50-69 years. Implementing this strategy for women aged 45-49 years and 70-74 years can be considered. Other screening strategies or additional examinations could be considered for women with high mammographic density; (c) cervical cancer using human papillomavirus (HPV) screening at intervals no shorter than 5 years for women aged 30-65 years. It is recommended to adapt policies according to vaccination status and screening history; and (d) lung cancer using annual low-dose computed tomography (LDCT) for individuals considered to be at increased risk of lung cancer based on age, history of smoking or validated risk models, with biennial screening as an alternative. Screening should incorporate smoking cessation interventions.

Although cancer is a leading cause of death in the European Union, around 40% of cases are preventable. The European Code Against Cancer (ECAC) was developed to inform citizens about key cancer-risk-reducing actions. This study aimed to identify effective ways to present the 5th edition of the code (ECAC5) to optimise awareness of cancer risks in all socioeconomic groups. Using a 2 × 3 × 2 factorial design, 10 027 participants from eight countries were randomised online to receive 'no message' or one of 10 ECAC5 formats differing in message content (cancer risks: present/absent), length of message on cancer prevention actions (longer/shorter/absent) or format (text-only/text with images). The primary outcome was awareness of 16 avoidable cancer risks. Overall mean number of risks recalled was 2.40 (standard deviation: 1.72; range 0-14). Recall was highest when messages included risk information. Adding prevention messages to risk information did not improve risk factor recall. Message length and images had no significant impact. Effects were similar across levels of education and countries. Combined information about risk factors and preventive actions has the potential to equitably increase citizens' very low cancer prevention awareness. How this awareness might change over time or lead to behaviour change is unknown and should be the focus of future evaluations.

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.

Diet, body weight, physical activity, sedentary behavior, and breastfeeding are modifiable factors influencing the cancer burden in the European Union, shaped by underlying social, commercial, environmental, and behavioral conditions. Excess body weight has reached epidemic levels, significantly influenced by widespread intake of sugar-sweetened beverages and ultra-processed foods rich in sugar, fat, and salt. Consumption of red and processed meat also commonly exceeds dietary recommendations. Physical inactivity and prolonged sedentary behavior are widespread. Breastfeeding rates vary widely across Europe but are generally low, particularly in high-income countries. To reduce cancer risk, the European Code Against Cancer, 5th edition (ECAC5) recommends a diet rich in whole grains, vegetables, legumes, and fruits, while limiting red meat and avoiding processed meat. Intake of vegetables, legumes, and fruits prevents aerodigestive tract cancers, while diets high in whole grains and low in red and processed meat reduce colorectal cancer risk. Avoiding excess body weight through diet and physical activity, and limiting prolonged sitting, decreases risk of numerous cancers. Promoting and supporting sustained breastfeeding contributes to lowering breast cancer risk. Key policy interventions, such as fiscal incentives, urban planning, marketing restrictions, and public awareness campaigns, are central to creating supportive environments for cancer prevention.

Occupational exposure to cancer-causing agents is a major, yet preventable, contributor to cancer in Europe and globally. In the European Union (EU), cancer is responsible for nearly half of all work-related deaths, underscoring the critical need for prevention measures. Effective strategies typically involve regulatory and workplace measures aimed at reducing or eliminating exposure risks. Raising awareness of hazardous workplace exposures is essential to empower individuals, foster a culture of prevention, and support effective regulation. The 5th edition of the European Code Against Cancer (ECAC5) includes a recommendation on how individuals can minimize their cancer risk and highlights the shared responsibilities of workers and employers for occupational safety and health: 'Inform yourself about cancer-causing factors at work and call on your employer to protect you against them. Always follow health and safety instructions at your workplace'. Key to ECAC5 is the addition of policy pointers at the governance level to support employers in taking preventive action and improving worker awareness. Strengthening regulatory frameworks and increasing awareness are crucial steps toward reducing the burden of occupational cancer.

The main infections that cause cancer in the European Union (EU) are Helicobacter pylori (H. pylori), human papillomavirus (HPV), hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Altogether, in 2022, these infections accounted for ~ 5% of all cancers in the EU, mainly of the stomach, cervix uteri and liver. The largest burden of infection-caused cancers was found in the south of the EU and near the eastern border. Substantial progress in the efficacy of interventions against these infections has been made since the release of the 4th edition of the European Code Against Cancer in 2015. Cancers due to infections can increasingly be prevented by prophylactic vaccines (HPV and HBV) and/or prompt diagnosis and treatment that can either cure (HCV and H. pylori) or slow down the infection (HBV and HIV), thus substantially reducing disease risk. Tools to tackle carcinogenic infections are also increasingly accessible and affordable in the EU, but their implementation is slow. Public awareness, political will and cost-effective protocols are necessary to establish large programmes of vaccination or testing and treatment. Progress monitoring, as well as avoiding disinformation and stigma, is crucial to ensure that advances in medical progress are fully leveraged. The recently published 5th edition of the European Code Against Cancer therefore recommends: (1) vaccinate girls and boys against HBV and HPV at the age recommended in your country; (2) take part in testing and treatment for HBV and HCV, HIV and H. pylori, as recommended in your country.

Knowledge mobilisation is essential in cancer prevention to equip individuals with the knowledge to reduce their risk and improve their health. Hence, dissemination of evidence-based recommendations is a key tenet in the fight to reduce the burden of cancer in the European Union (EU). Systems thinking was used to guide the methods of three substudies involving stakeholders in identifying dissemination actions to enhance the awareness and uptake of the European Code Against Cancer, 5th edition (ECAC5), including mapping barriers and facilitators to achieve impactful dissemination. The proposed actions aimed to foster collaboration and partnership across diverse sectors, utilising diverse and accessible channels to deliver visually engaging content to maximise the delivery and impact of the ECAC5 to the general public in the EU. Many of these actions were evaluated by participants as highly feasible and impactful, thereby supporting their implementation.

The European Code Against Cancer (ECAC) provides evidence-based recommendations to help individuals reduce their cancer risk. For the 5th edition (ECAC5), recommendations on ultraviolet radiation (UVR) and indoor radon exposures were updated, and complementary recommendations for policymakers were introduced. UVR and radon are classified as carcinogenic to humans (group 1 carcinogens) in the International Agency for Research on Cancer (IARC) Monographs. Solar UVR and, to a lesser extent, artificial forms of UVR exposure are major causes of skin cancer, while radon gas is a leading cause of lung cancer. This paper summarises the evidence for retaining and refining these recommendations. For individuals, ECAC5 advises avoiding excessive sun exposure, especially in children, using sun protection, and never using sunbeds; for radon, checking local radon maps, seeking professional measurement where appropriate and taking remedial action, if necessary, are recommended. For policymakers, ECAC5 encourages harmonised UVR protection measures across the European Union, enforcement of regulations concerning indoor tanning devices, and enabling access to testing of radon levels, and support for mitigation and remediation. These recommendations provide actionable, evidence-based recommendations to help reduce cancer risk and align with Europe's Beating Cancer Plan.

Combining chemotherapy with chemosensitizing agents is a common strategy to enhance anticancer efficacy while mitigating treatment-related side effects. This study investigated the potential of dammarenediol II (DM2), a ginsenoside precursor, to enhance the anticancer effects of etoposide by downregulating O-linked β-N-acetylglucosamine modification (O-GlcNAcylation) and modulating the Akt signaling pathway in HepG2 human liver cancer cells. The effect of DM2 on O-GlcNAcylation regulation was analyzed using Pharmaco-Net, an artificial intelligence-driven drug screening platform and further validated using O-GlcNAc transferase (OGT) activity assay. DM2 cotreatment enhanced etoposide's anticancer efficacy, which was quantitatively evaluated by viability, Annexin V binding, membrane integrity, and caspase-3/7 activity assays in HepG2 cells. Results showed that DM2 reduced O-GlcNAc levels by directly interacting with OGT, as confirmed through Pharmaco-Net. Cotreatment with 40 μm DM2 and 20 μm etoposide produced synergistic anticancer effects, lowering etoposide's IC₅₀ for cell viability by 2.29-fold and its EC₅₀ for caspase-3/7 activity by 3.64-fold. Mechanistically, DM2 dose-dependently suppressed Akt/GSK3β/mTOR signaling. Using the Akt activator SC79, additional experiments confirmed that Akt signaling acts downstream of O-GlcNAcylation regulated by etoposide and DM2. These effects were also observed in multiple human liver cancer cell lines, as well as in A549 lung and Caco-2 colorectal cancer cells. This supports the broader anticancer and Akt-inhibitory potential of DM2. This study is the first to demonstrate that DM2 enhances anticancer synergy by suppressing O-GlcNAcylation and Akt signaling, highlighting its potential as a novel chemotherapy adjuvant.

Plecstatin (PST) is a potent anticancer agent in preclinical models, yet its precise mechanism of action and molecular specificity regarding its main targets, plectin and outer dense fiber protein 2 (ODF2), remain incompletely understood. Here, we dissected PST's mode of action using knockouts of plectin (PLEC) and ODF2 in SNU-475 hepatocellular carcinoma (HCC) cells. PST suppressed anchorage-independent growth and impaired 2D and 3D migration in a dose-dependent manner in both wild-type and ODF2-deficient cells, but not in PLEC-deficient cells, establishing plectin as the principal effector of PST's antitumor activity. Proteomic and functional analyses revealed that PST primarily disrupts cytoskeletal remodeling through plectin, while selectively affecting ciliogenesis-related pathways linked to ODF2 loss. Deletion of either protein attenuated PST-induced Ser51 phosphorylation of eIF2α, ATF4/GADD34 induction, and cytochrome c release, indicating cooperative involvement in integrated stress response (ISR). Correlative analysis of patient datasets confirmed associations between PLEC/ODF2 expression and ISR-related gene signatures, supporting the clinical relevance of this pathway. Together, these findings identify plectin as a key target of PST in disrupting cytoskeletal integrity and establish plectin/ODF2 axis in PST-driven stress adaptation in HCC.