Medical Oncology最新文献

{"title":"Combination therapy using parthenolide and doxorubicin induces apoptosis in Raji cells: insights into miR-27b and signaling pathway alterations.","authors":"Zahra Zare-Badie, Farahnaz Zare, Banafsheh Rastegari, Gholamhossein Tamaddon","doi":"10.1007/s12032-025-02673-w","DOIUrl":"10.1007/s12032-025-02673-w","url":null,"abstract":"<p><p>Burkitt lymphoma, a highly aggressive form of non-Hodgkin lymphoma, have significant treatment challenges, such as chemotherapy-related toxicity and the risk of relapse, especially in older adults. Treatment of Raji cells, a Burkitt lymphoma cell line, with parthenolide in combination to doxorubicin may enhance therapeutic efficacy. This study aimed to evaluate cell viability and apoptosis following treatment with these agents, and to investigate the underlying molecular mechanisms involving miR-27b and the MET/PI3K/AKT signaling pathway. Raji cells were treated with varying concentrations of parthenolide and doxorubicin for 48 and 72 h, cell viability was assessed using the MTT assay, and apoptosis was quantified using flow cytometry. Subsequently, we performed quantitative RT-PCR to evaluate the expression levels of miR-27b, MET, PI3K, and AKT. The half-maximum inhibitory concentration (IC₅₀) values of 976.1 nM for doxorubicin and 4.39 µM for parthenolide were determined at 48 h. The apoptosis rate increased from 7.6% in the untreated control to 44.5% and 49.2% for doxorubicin and parthenolide, respectively, reached to 81.2% at higher doses of parthenolide in combination (p < 0.001). miR-27b expression was significantly upregulated, particularly in the combination group (p < 0.001). MET and PI3K expression was significantly downregulated by the combination treatments (p < 0.05). In conclusion, combination of parthenolide and doxorubicin exert enhanced cytotoxic effects via increased apoptosis and modulation of miR-27b and the MET signaling pathway in Raji cells, regulatory relationship between miR-27b and the MET signaling pathway may contribute to the observed therapeutic benefits. Further research is required to clarify the molecular mechanisms and therapeutic applications of this combination strategy.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 4","pages":"99"},"PeriodicalIF":2.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143616233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advancements in genistein nanocarrier systems for effective cancer management.","authors":"Diya Arora, Vanshita, Hemant Bhati, Keshav Bansal","doi":"10.1007/s12032-025-02649-w","DOIUrl":"10.1007/s12032-025-02649-w","url":null,"abstract":"<p><p>Cancer continues to be a significant global health concern, consistently ranking as one of the leading causes of mortality across diverse populations and socio-economic contexts. Genistein, a soy-derived isoflavonoid, has gained significant attention for its diverse health benefits, particularly its potent anticancer activity. Emerging pre-clinical and clinical evidences highlights its ability to modulate key cellular processes, including apoptosis, autophagy, angiogenesis, metastasis, immune responses and cell cycle regulation. Despite its therapeutic potential, the clinical translation of genistein is limited by its poor pharmacokinetics, low aqueous solubility, and rapid metabolic degradation, resulting in suboptimal bioavailability. To address these limitations, various nanotechnology-based formulations have been developed, significantly improving the bioavailability, stability, and therapeutic efficacy of genistein. Functionalized nanocarriers further enhance its effectiveness by enabling targeted drug delivery, reducing off-target toxicities, and achieving sustained release at the tumor site. This review provides a comprehensive overview of advanced nanoformulations for genistein delivery emphasizing their efficacy against prevalent cancers such as breast, lung, and colon cancer. By exploring the interplay between genistein's therapeutic potential and innovative drug delivery systems, this review underscores the transformative impact of nanotechnology in overcoming the limitations of conventional cancer therapies and improving patience compliance.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 4","pages":"101"},"PeriodicalIF":2.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143616268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PKM2 knockout facilitates the activation of the AMPK/KLF4/ACADVL pathway, leading to increased oxidative degradation of fatty acids in TNBC.","authors":"Linghan Zhang, Li Cheng, Yingchao Ma, Junlin Li, Yue Zhong, Xiuzhi Zhu, XiaoMin Leng, Fuhua Xie","doi":"10.1007/s12032-025-02671-y","DOIUrl":"10.1007/s12032-025-02671-y","url":null,"abstract":"<p><p>This study unveils PKM2 as a master metabolic coordinator in triple-negative breast cancer (TNBC), governing the glycolysis-lipolysis balance through the AMPK/KLF4/ACADVL axis. We demonstrate stage-specific PKM2 upregulation in TNBC, with CRISPR/Cas9 knockout inducing dual metabolic reprogramming-suppressed glycolysis and activated lipid catabolism. Mechanistically, PKM2 ablation triggers AMPK-dependent nuclear translocation of KLF4, which directly activates ACADVL (mitochondrial β-oxidation rate-limiting enzyme), explaining lipid droplet depletion. Therapeutically, synergistic lethality emerges from combining PKM2 knockout with ACADVL inhibition, suggesting metabolic redundancy disruption strategies. Unlike PKM2-SCAP-mediated lipogenesis reported elsewhere, our work establishes a KLF4-driven lipid catabolic pathway specific to TNBC. Crucially, this AMPK/KLF4/ACADVL network operates independently of BRCA status, proposing targeted therapy for chemoresistant non-BRCA mutant TNBC. Our findings redefine TNBC metabolic plasticity through transcriptional-metabolic crosstalk, offering combinatorial therapeutic paradigms against metabolic adaptation.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 4","pages":"102"},"PeriodicalIF":2.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143616261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomal RNAs and EZH2: unraveling the molecular dialogue driving tumor progression.","authors":"Ahmed Hussein Zwamel, Abdulrahman T Ahmad, Farag M A Altalbawy, H Malathi, Amandeep Singh, Majid S Jabir, Zafar Aminov, Madan Lal, Abhinav Kumar, Sabrean F Jawad","doi":"10.1007/s12032-025-02648-x","DOIUrl":"10.1007/s12032-025-02648-x","url":null,"abstract":"<p><p>The EZH2 gene encodes an enzyme that is part of the epigenetic factor Polycomb Repressive Complex 2 (PRC2). In order to control gene expression, PRC2 mainly modifies chromatin structure. In this complex process, EZH2 methylates histone proteins, which in turn suppresses further RNA transcriptions. As a result, EZH2 dysregulations can occasionally induce abnormal gene expression patterns, which can aid in the development and progression of cancer. Non-coding RNAs significantly impact the expression of EZH2 through epigenetic mechanisms. Meanwhile, normal and cancerous cells frequently release vesicles into the extracellular matrix, also known as exosomes, that occasionally carry RNA molecules from their origin cells, including messenger RNAs, microRNAs, and other non-coding RNAs. Thus exosomes are granted the ability to regulate numerous physiological functions and act as crucial messengers between cells by influencing gene expression in the recipient cell. We conducted this review to focus on EZH2's substantial biological role and the mechanisms that regulate it, driven by the desire to understand the possible impact of exosomal RNAs on EZH2 expression.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 4","pages":"103"},"PeriodicalIF":2.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143616236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fisetin as a chemoprotective and chemotherapeutic agent: mechanistic insights and future directions in cancer therapy.","authors":"Rabab Fatima, Priyal Soni, Mousmee Sharma, Parteek Prasher, Rajesh Kaverikana, Shivaprasad Shetty Mangalpady, Javad Sharifi-Rad, Daniela Calina","doi":"10.1007/s12032-025-02664-x","DOIUrl":"10.1007/s12032-025-02664-x","url":null,"abstract":"<p><p>Cancer remains a leading cause of mortality globally, characterized by the uncontrolled proliferation of abnormal cells, invasion of healthy tissues, and potential metastasis. Natural compounds have become a focus in cancer research due to their potential therapeutic roles. Among these, fisetin, a dietary flavonoid, demonstrates notable anti-cancer properties through various molecular mechanisms. This review evaluates the chemoprotective and chemotherapeutic potential of fisetin, focusing on its mechanisms of action against cancer and its capacity to enhance cancer treatment. A systematic literature search was conducted across PubMed, Web of Science, and Scopus databases using keywords related to fisetin and cancer. The review synthesizes findings from in vitro and in vivo studies examining fisetin's effects on signaling pathways, apoptosis induction, oxidative stress modulation, and synergistic potential with chemotherapeutic agents. Fisetin has shown the ability to suppress tumor growth and metastasis by modulating critical signaling pathways, including PI3K/Akt/mTOR, NF-κB, and MAPK. It induces apoptosis in cancer cells through mitochondrial and endoplasmic reticulum stress responses and demonstrates antioxidative properties by reducing reactive oxygen species. Additionally, fisetin enhances the efficacy of conventional chemotherapies, indicating its role as a potential adjuvant in cancer treatment. Fisetin presents a promising natural compound with diverse anti-cancer effects, impacting cell cycle arrest, apoptosis, and oxidative stress pathways. Further clinical studies are warranted to fully elucidate its therapeutic potential and to optimize its delivery for improved bioavailability in cancer patients.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 4","pages":"104"},"PeriodicalIF":2.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143616238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative approach to decipher pharmacological mechanism of Cinnamomum zeylanicum essential oil in prostate cancer.","authors":"Debajani Mohanty, Sucheesmita Padhee, Arpita Priyadarshini, Rout George Kerry, Biswabhusan Dash, Ambika Sahoo, Sudipta Jena, Pratap Chandra Panda, Haseeb Ahmad Khan, Sanghamitra Nayak, Asit Ray","doi":"10.1007/s12032-025-02665-w","DOIUrl":"10.1007/s12032-025-02665-w","url":null,"abstract":"<p><p>Prostate cancer has garnered much importance in recent years due to its rising incidence and mortality among men worldwide. The ineffectiveness of existing therapies and adverse events associated with conventional treatment have led patients to turn towards traditional medicine for the management of prostate cancer. Cinnamomum zeylanicum bark essential oil (CZEO) possesses promising anticancer properties, yet the exact mechanism of action of CZEO for the management of prostate cancer remains unclear. Therefore, the current study tried to elucidate the bioactive components and key potential targets through which CZEO may exert its anticancer effect for treating prostate cancer. Fifty-nine constituents were identified by GC-MS, of which 52 were drug-like constituents. A total of 2847 targets related to CZEO and 2283 targets related to prostate cancer were obtained from public databases and the GEO dataset. Twenty-three overlapping targets exist between CZEO and disease targets. Compound-disease-target network analysis revealed camphor, eugenol, methyl eugenol, trans farnesyl acetate and nerol as the core bioactive ingredients of CZEO. The topological screening of the PPI network revealed BCL2, TNF, NFKBIA, CREBBP and IL7R as potential hub targets. These hub targets were validated based on mRNA expression level, pathological stages, overall survival, immune infiltrate and genetic alteration analysis in prostate adenocarcinoma and normal patients. KEGG enrichment analysis proposed that CZEO exhibits its anticancer effect mainly by modulating the PI3-AKT and MAPK signalling pathway. Moreover, molecular docking and dynamics simulation studies revealed a good binding affinity of these core compounds with TNF, NFKBIA and BCL2. CZEO exhibited a remarkable anti-proliferative effect against PC-3 cells with an IC₅₀ value of 13.56 µg/mL. CZEO promoted apoptosis and cell cycle arrest in the G2/M phase in PC-3 cells. CZEO-induced apoptosis was due to loss of mitochondrial membrane potential, increase in reactive oxygen species levels and activation of caspases (caspase 3, caspase 8 and caspase 9). RT-qPCR analysis revealed that CZEO modulated the mRNA expression level of hub genes (BCL2, TNF, NFKBIA, CREBBP, and IL7R, caspase 3, caspase 8 and caspase 9). The present study provides a mechanistic approach of Cinnamomum zeylanicum essential oil against prostate cancer.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 4","pages":"100"},"PeriodicalIF":2.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143616259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FBXO32 ubiquitination of SUFU promotes progression and lenvatinib resistance in hepatocellular carcinoma via hedgehog signaling.","authors":"Shunyi Wang, Rui Peng, Chen Chen, Daoyuan Tu, Jun Cao, Bingbing Su, Songsong Fan, Yangyang Miao, Chi Zhang, Guoqing Jiang, Shengjie Jin, Dousheng Bai","doi":"10.1007/s12032-025-02644-1","DOIUrl":"10.1007/s12032-025-02644-1","url":null,"abstract":"<p><p>Lenvatinib is a prevalent treatment for hepatocellular carcinoma (HCC), yet resistance to the drug significantly limits its effectiveness. This study investigates the role of FBXO32 (F-Box Protein 32) in HCC progression and lenvatinib resistance. Methods: We utilized the GSE211850 and GSE46408 datasets to identify an E3 ubiquitin ligase that is highly expressed in both lenvatinib-resistant HCC cells and HCC tissues. The expression and clinical relevance of this E3 ubiquitin ligase were further validated using lenvatinib-resistant HCC cells, online databases, and HCC clinical tissue samples. The phenotype was verified by cell and animal experiments. Techniques such as RNA sequencing, western blotting, immunofluorescence, Co-immunoprecipitation (Co‑IP), Ubiquitination, and cycloheximide (CHX) chase assay reveal the mechanism. FBXO32 is highly expressed in both lenvatinib-resistant HCC cells and HCC tissues. High FBXO32 expression correlated with increased ALT, AFP levels, larger tumors, and advanced TNM stages, serving as an independent risk factor for overall survival (OS) and recurrence-free survival (RFS). Functional assays demonstrated that FBXO32 overexpression enhanced cell proliferation, stemness, apoptosis resistance, and lenvatinib resistance, while knockdown had opposing effects. KEGG enrichment analysis indicated a link between FBXO32 and the Hedgehog signaling pathway. FBXO32-mediated degradation of SUFU, a Hedgehog pathway inhibitor, activated this pathway. Inhibiting Hedgehog signaling counteracted FBXO32's impact on HCC growth and resistance. Conclusion: FBXO32 is a critical marker for lenvatinib efficacy and HCC prognosis, suggesting that targeting FBXO32 or the Hedgehog pathway could provide innovative strategies for overcoming lenvatinib resistance in HCC.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 4","pages":"98"},"PeriodicalIF":2.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting EGFR and PI3K/mTOR pathways in glioblastoma: innovative therapeutic approaches.","authors":"Gursimran Singh, Rohit, Pankaj Kumar, Khadga Raj Aran","doi":"10.1007/s12032-025-02652-1","DOIUrl":"10.1007/s12032-025-02652-1","url":null,"abstract":"<p><p>Glioblastoma (GBM) stands as the most aggressive form of primary brain cancer in adults, characterized by its rapid growth, invasive nature, and a robust propensity to induce angiogenesis, forming new blood vessels to sustain its expansion. GBM arises from astrocytes, star-shaped glial cells, and despite significant progress in understanding its molecular mechanisms, its prognosis remains grim. It is frequently associated with mutations or overexpression of the epidermal growth factor receptor (EGFR), which initiates several downstream signaling pathways. Dysregulation of key signaling pathways, such as EGFR/PTEN/AKT/mTOR, drives tumorigenesis, promotes metastasis and leads to treatment resistance. The modest survival benefits of the conventional treatment of surgical resection followed by radiation and chemotherapy underscore the pressing need for innovative therapeutic approaches. In most the tumor, overexpression of EGFR is found associated with GBM and mutations in its several variants are important for promoting ongoing mitogenic signaling and tumor growth. This receptor inhibits apoptosis and promotes cell survival and proliferation by activating downstream PI3K/AKT/mTOR pathways. This route is typically blocked by PTEN, a crucial tumor suppressor, however, GBM frequently results in abnormalities in this protein. The aim of this review is to explore the molecular foundations of GBM, with a focus on the EGFR and PI3K/mTOR pathways and their impact on tumor behavior. Additionally, this review highlights EGFR and PI3K/AKT/mTOR inhibitors currently in clinical and preclinical trials, addressing treatment resistance, challenges, and future directions.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 4","pages":"97"},"PeriodicalIF":2.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomal miR-92a-3p modulates M2 macrophage polarization in colorectal cancer: implications for tumor migration and angiogenesis.","authors":"Wei Zhao, Yudan Wu, Yixiao Wang, Tongyi Li, Qiuyan Liu, Zhiping Hou","doi":"10.1007/s12032-025-02635-2","DOIUrl":"10.1007/s12032-025-02635-2","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is one of the most prevalent malignant neoplasms globally. Its development and metastasis are closely associated with the polarization of macrophages within the tumor microenvironment (TME). In particular, the polarization of M2-type macrophages has been demonstrated to be related to the promotion of tumor growth, migration, and angiogenesis. This study aims to investigate the role of miR-92a-3p in colon cancer-derived exosomes in regulating M2-type macrophage polarization by targeting EID2B and to elucidate the impact of this process on tumor migration and angiogenesis. MicroRNAs that were differentially expressed in plasma exosomes from CRC patients were initially identified through a search of the GEO database. The results were then verified by RT-qPCR using miR-92a-3p. The uptake of exosomes was observed via laser confocal microscopy, and the impact of miR-92a-3p on the polarization of exosomes and macrophages was examined through the use of RT-qPCR and WB. A bioinformatics analysis and a dual-luciferase reporter assay were employed to identify the downstream target of miR-92a-3p and to investigate its effect on the MAPK/ERK pathway. miR-92a-3p was upregulated in plasma exosomes of colon cancer patients and exhibited a positive correlation with lymph node metastasis. The results demonstrated that miR-92a-3p was capable of promoting M0 macrophage polarization toward the M2 phenotype, and of enhancing the migratory and invasive capacities of CRC cells, as well as their angiogenic potential in vitro. Bioinformatic analysis and experimental validation demonstrated that miR-92a-3p targeted EID2B and that this target gene was negatively correlated with M2-type macrophage polarization. The results demonstrated that miR-92a-3p promotes macrophage M2 polarization by activating the MAPK/ERK pathway. miR-92a-3p activates the MAPK/ERK pathway and induces macrophage M2 polarization by targeting EID2B, thereby promoting migration and angiogenesis in CRC. These findings offer new potential targets for the treatment of colon cancer.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 4","pages":"96"},"PeriodicalIF":2.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Young-onset metastatic colorectal cancer: an opportunity and a vision for progress in cancer.","authors":"Prasad D Cooray, Nicole Jane Cooper","doi":"10.1007/s12032-025-02640-5","DOIUrl":"10.1007/s12032-025-02640-5","url":null,"abstract":"<p><p>Metastatic young-onset colorectal cancer (yo-CRC) is a distinct and aggressive disease subtype that is becoming increasingly prevalent worldwide with Australia leading the world in this trend. This article provides an evidence-based perspective, through the prism of authors' personal experience, to craft an effective pathway not only to deliver improved outcomes for the patients but also to reduce disparities and foster collaboration amongst the cancer-treating community and indeed patients. It highlights an opportunity to re-define, re-design, and create a model that is rewarding to patients and cancer-treating community. Although our focus is on the high unmet needs group of yo-CRC, this model has the potential to expand to other cancer types and care models. We analyse the unique epidemiological trends, challenges, and burdens, emphasising the need for tailored treatment approaches for younger patients with colorectal cancer especially in the metastatic setting. We identify current gaps in clinical practice and research. To improve real-world outcomes, we propose a conceptual framework to enhance clinician-patient communication and treatment planning. Central to our approach is the integration of a Registry of Incidence, Intervention, and Outcomes (RIIO), which enables real-time data collection and analysis, improving treatment personalisation and efficacy. This registry could revolutionise patient care and drive research innovation through enhanced data sharing and collaboration. We advocate for a patient-centric integrated care model that utilises all available therapies to maximise survival and quality of life. Our perspective underscores the urgent need for a paradigm shift in how yo-CRC is viewed, researched and managed, proposing a pathway to significantly enhanced outcomes. Whilst it is feasible to expand the concepts discussed here for all colorectal cancer and indeed all cancer types, we believe this approach is most relevant and acutely needed in yo-CRC setting for reasons detailed in the manuscript.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 4","pages":"95"},"PeriodicalIF":2.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}