The shortage of well-trained personnel to deliver cancer care and conduct research remains a major obstacle to reducing disparities in cancer survival between high-income countries and low-income and middle-income countr...The shortage of well-trained personnel to deliver cancer care and conduct research remains a major obstacle to reducing disparities in cancer survival between high-income countries and low-income and middle-income countries (LMICs). This Commission set out to provide actionable guidance for strengthening the global cancer workforce with an emphasis on reducing these disparities. To better understand the extent of the rising global cancer burden and the resulting workforce needs, we modelled the current and future global landscape of 17 common cancers and 18 workforce personnel types. Among the modelled cancers, diagnosed incidence rates are projected to increase globally, especially in LMICs, driven by growing and ageing populations and changing risk factors. Crucially, we estimate that one in three cancers go undiagnosed worldwide, with more than 60% of cancers remaining undiagnosed in parts of Africa. We find that, among the diagnosed cancers in LMICs, late-stage presentation and a lack of essential treatments and qualified health professionals contribute to poor survival. According to our modelling, in 2050, 5-year net survival is projected to remain lowest in Africa (34%) and Asia (39%), while reaching beyond 60% in high-income settings. The global cancer workforce shortage is projected to reach about 100 million in 2050, with the largest shortages being for nurses (65 million) and diagnostic (radiology and pathology) specialists (16 million), especially in Africa and Asia. Comprehensive workforce scale-up of all personnel types is projected to avert 170 million cancer deaths and yield net economic benefits of US$120 trillion between 2030 and 2050, translating to a global return on investment of $4 per $1 invested. Focusing primarily on examples from sub-Saharan Africa and Latin America, we examine key obstacles to workforce development and retention in LMICs and propose pragmatic actions to address the workforce crisis. These actions include establishment of workforce and cancer registries; the creation of cross-sector and international partnerships to improve access to education and research training programmes as well as diagnostics, therapeutics, and equipment; and implementation of task-shifting, digital health, and artificial intelligence solutions, which could improve workforce productivity, further strengthening the case for investing in the cancer workforce. TRANSLATIONS: For the Spanish, Portuguese, French, Chinese (Mandarin), Arabic and Russian translations of the abstract see Supplementary Materials section.
Komura G, Kuzuya T, Muto H
… +13 more, Tachi Y, Kobayashi M, Sugiyama H, Ariga M, Morisaki S, Nakano T, Tanaka H, Nakaoka K, Ohno E, Funasaka K, Nagasaka M, Miyahara R, Hirooka Y
INTRODUCTION: Real-world evidence is limited for patients with unresectable hepatocellular carcinoma (HCC) who are ineligible for locoregional therapy (LRT) at initial diagnosis. We examined diagnostic pathways and outco...INTRODUCTION: Real-world evidence is limited for patients with unresectable hepatocellular carcinoma (HCC) who are ineligible for locoregional therapy (LRT) at initial diagnosis. We examined diagnostic pathways and outcomes of first-line atezolizumab plus bevacizumab (Atz+Bev), with a focus on de novo LRT-ineligible HCC. METHODS: We retrospectively analyzed 107 systemic therapy-naïve patients with unresectable HCC who received Atz+Bev as first-line systemic therapy. Patients were categorized into LRT-naïve (n = 55) and LRT-experienced (n = 52) groups. Diagnostic pathways, baseline characteristics, and treatment outcomes were evaluated. RESULTS: Among LRT-naïve patients, 34.5% presented with HCC-related symptoms, whereas the majority were diagnosed incidentally during outpatient care for metabolic comorbidities, often triggered by mild liver enzyme abnormalities. In this group, clinically meaningful disease control was observed despite a high intrahepatic tumor burden at presentation, with an objective response rate of 41.8% and a disease control rate of 87.3%. Median progression-free survival was 11.7 months. Clinical outcomes were generally comparable between the LRT-naïve and LRT-experienced groups. CONCLUSION: Atz+Bev provides clinically meaningful disease control in patients presenting with de novo LRT-ineligible unresectable HCC. The frequent incidental mode of diagnosis highlights opportunities to strengthen risk stratification and surveillance in high-risk metabolic liver disease.
Curr Treat Options Oncol
· 2026 May · PMID 42213241
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As survival among reproductive-age patients with breast cancer continues to improve with modern therapies, concerns regarding fertility preservation, gonadotoxicity, and pregnancy safety have become increasingly prominen...As survival among reproductive-age patients with breast cancer continues to improve with modern therapies, concerns regarding fertility preservation, gonadotoxicity, and pregnancy safety have become increasingly prominent. Fertility considerations are well-recognized contributors to treatment refusal and premature discontinuation, therefore, oncofertility counselling should be initiated at diagnosis and integrated into therapeutic planning. Prompt referral for fertility preservation is essential for patients who may wish to conceive, without compromising oncologic outcomes. Systemic therapy selection should remain driven by tumour biology and recurrence risk; however, when clinically equivalent regimens are available, those with lower gonadotoxic potential are preferred. Cytotoxic chemotherapy is the main determinant of permanent ovarian insufficiency, and temporary ovarian suppression during chemotherapy should be routinely considered in appropriate candidates. Endocrine therapy is not associated with irreversible ovarian damage, but its long duration necessitates individualized planning for pregnancy, including supervised treatment interruption in selected low-risk patients. HER2-monoclonal antibodies should be delivered according to standard indications, as it does not appear to confer substantial additional ovarian toxicity beyond chemotherapy; however, pregnancy must be avoided during treatment. For antibody-drug conjugates, PARP inhibitors, and CDK 4 and 6 inhibitors, the absence of prospective human fertility data supports a precautionary approach, including pre-treatment fertility preservation, effective contraception during therapy, and adherence to recommended washout periods. Given the substantial gaps in clinical evidence, transparent communication of uncertainty is essential. The integration of standardized reproductive endpoints into clinical trials, alongside the development of predictive tools is critical to support evidence-based counselling and optimize long-term survivorship outcomes.
OBJECTIVES: The cancer diagnostic process may be more complicated for patients with a learning disability ('intellectual disability' outside of the UK) than for other patients. We aimed to investigate whether patients wi...OBJECTIVES: The cancer diagnostic process may be more complicated for patients with a learning disability ('intellectual disability' outside of the UK) than for other patients. We aimed to investigate whether patients with a learning disability were more likely to experience disadvantage in cancer diagnostic pathways and outcomes. DESIGN: A retrospective cohort study using routinely collected linked data across primary care and cancer registration. SETTING: 1470 general practices in England. PARTICIPANTS: 277 050 participants who were aged 40+ years, had an incident cancer recorded in the cancer registration during 2012-2018 and were registered for at least 3 years at their general practice prior to diagnosis. MAIN OUTCOME MEASURES: Emergency presentation route to diagnosis or urgent suspected cancer referral route to diagnosis, cancer stage at diagnosis (early vs advanced) and all-cause mortality within 30 days after diagnosis. RESULTS: 277 050 patients were included in the overall study, of which 211 423 were included in analyses with cancer stage as outcome. Learning disability was recorded for 796 (0.3%) patients. Patients with a learning disability were over twice as likely to be diagnosed via an emergency presentation (adjusted OR (aOR): 2.65, 95% CI 2.26 to 3.11, p<0.001) and half as likely to be diagnosed via an urgent suspected cancer referral (aOR: 0.51, 95% CI 0.43 to 0.60, p<0.001). They were also more likely to be diagnosed with advanced-stage cancer (aOR: 1.37, 95% CI 1.12 to 1.67, p=0.002), especially for breast cancer, and to die within 30 days of diagnosis (aOR: 3.77, 95% CI 3.10 to 4.59, p<0.001) than patients without a learning disability. CONCLUSIONS: Patients with a learning disability experience marked inequalities in cancer diagnostic pathways and outcomes. The increased risk of advanced-stage breast cancer is of particular note. Improved support to access and navigate the health care system may be required to negate experienced difficulties during the diagnostic process.
OBJECTIVE: National guidelines recommend that people with advanced stage non-small cell lung cancer (NSCLC) and good performance status (PS 0-1) are offered systematic anticancer therapy (SACT). This study investigated p...OBJECTIVE: National guidelines recommend that people with advanced stage non-small cell lung cancer (NSCLC) and good performance status (PS 0-1) are offered systematic anticancer therapy (SACT). This study investigated patterns of SACT use among patients with advanced NSCLC within England. METHODS AND ANALYSIS: The study used data on patients with stage 3B-4B NSCLC diagnosed between 2019 and 2022 identified from the Rapid Cancer Registration Dataset. Linkage to other national datasets provided information on SACT use and hospital admissions. Regression models were used to assess the association between patient characteristics and treatment patterns and to explore variation in practice between cancer alliances. Survival analysis was used to estimate the potential life-years gained if all cancer alliance treatment rates matched the highest rate of SACT use. RESULTS: The study analysed 60 210 patients diagnosed with advanced NSCLC in England (2019-2022). PS was good (=0/1) in 43% of patients; of these, 62% received SACT. Receipt of SACT decreased as age at diagnosis increased, in patients with stage 4 disease (vs 3B/C), among patients who lived in more deprived areas and among patients with a greater burden of comorbidity or more severe frailty. After adjusting for patient characteristics, use of SACT ranged from around 50% to 70% between cancer alliances. If all cancer alliances achieved the highest alliance treatment rate, a further 448 patients would be treated each year, with 289 life-years gained. CONCLUSION: For English patients with advanced NSCLC (PS=0/1), use of SACT is strongly associated with age, frailty and socio-economic deprivation. Substantial variation in SACT use persists across Cancer Alliances, even after adjusting for patient characteristics. Addressing this variation could improve equity and population-level outcomes.
Bentayebi K, Louati S, Suwan K
… +2 more, Eljaoudi R, Hajitou A
Mol Ther Oncol
· 2026 Jun · PMID 42199604
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Medulloblastoma accounts for approximately 20% of all pediatric brain tumors. Standard treatment typically involves a multimodal approach including surgery, radiation therapy, and chemotherapy. Despite advances in molecu...Medulloblastoma accounts for approximately 20% of all pediatric brain tumors. Standard treatment typically involves a multimodal approach including surgery, radiation therapy, and chemotherapy. Despite advances in molecular classification and the development of targeted therapies, long-term survival and quality of life remain suboptimal, particularly for patients with high-risk subgroups. Although targeted therapies hold significant promise, their effective delivery to the brain remains a major challenge. The unique cerebellar microenvironment, including the blood-brain barrier, the blood-brain-tumor barrier, and the blood-cerebrospinal fluid barrier, restricts drug penetration and therapeutic efficacy. To overcome these limitations, innovative strategies are being explored to bypass or transiently modulate these barriers in a subgroup- and compartment-specific manner. These approaches include nanoparticle-based delivery systems, focused ultrasound, intrathecal administration, and rational combination therapies. Emerging platforms such as transmorphic phage/adeno-associated virus vectors and lysosomal targeting strategies are under active investigation and may further enhance therapeutic precision. This review provides a comprehensive overview of current brain-targeted drug delivery systems for medulloblastoma, highlighting barrier heterogeneity, recurrence patterns, and emerging technologies with the potential to improve therapeutic efficacy and long-term outcomes for children affected by this aggressive pediatric brain tumor.
Xu H, Wan MCT, Wong CCC
… +4 more, Qin S, Wen Y, Wang J, Chen Z
Mol Ther Oncol
· 2026 Jun · PMID 42179971
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Nicotinamide mononucleotide (NMN) supplementation has shown clinical benefits by regulating metabolic activities in the energy production process. Its protective effect and underlying immune regulatory mechanisms against...Nicotinamide mononucleotide (NMN) supplementation has shown clinical benefits by regulating metabolic activities in the energy production process. Its protective effect and underlying immune regulatory mechanisms against tumor progression are still poorly understood. Here, we found that the high-dose NMN treatment could alter the level of several key NAD metabolic enzymes in human immune cells. Moreover, high-dose NMN treatment exhibited comparable antitumor efficacy as the PD-1 blockade in the murine mesothelioma challenge model. Subsequent immune profiling in both secondary lymphoid organ and tumor demonstrated that, rather than modulating T cell and NK cell responses, high-dose NMN treatment could reset tumor-associated macrophages toward the inflammatory M1-like phenotype compared with PD-1 blockade or non-treated subjects. These results provided a better understanding of NMN's regulatory effect on immune cells and suggested an alternative strategy of cancer immunotherapy.
Mooney R, Ngai G, Kaur G
… +17 more, Kang EY, Lara J, Abd El-Fattah EE, Huang P, Flores L, McDonald M, Talley M, Hammad M, Laidlaw M, Alamillo A, Nguyen DH, Lesniak MS, Curiel DT, Kortylewski M, Santidrian AF, Dellinger T, Aboody KS
Mol Ther Oncol
· 2026 Jun · PMID 42179969
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Ovarian cancer (OVCA) is an aggressive and often recurrent malignancy with limited long-term responses to standard chemotherapy. To address the urgent need for novel, targeted therapies, we evaluated the efficacy of a tu...Ovarian cancer (OVCA) is an aggressive and often recurrent malignancy with limited long-term responses to standard chemotherapy. To address the urgent need for novel, targeted therapies, we evaluated the efficacy of a tumor-tropic neural stem cell (NSC) platform delivering a conditionally replicative adenovirus (CRAd), NSC.CRAd-S-pk7, in preclinical models of advanced OVCA. A single intraperitoneal dose of NSC.CRAd-S-pk7 delivering 3 × 10 infectious units (IFUs) significantly reduced tumor burden and increased median survival by 33% (from 57 to 76 days) in immunocompetent mice, and 48% (from 54 to 80 days) in immunodeficient mice bearing OVCA peritoneal metastases. No observed adverse effects occurred at or below this dose. Optimization of the NSC transduction protocol enabled at least a 10-fold increase in CRAd-S-pk7 viral payload per cell, reducing the therapeutic cell dose by more than an order of magnitude-from 60 million to just 1 million NSCs. Repeated dosing further decreased tumor burden and increased median survival by 60% (from 57 to 91 days) in immunocompetent mice, suggesting a contribution from innate immune activation. These findings establish NSC.CRAd-S-pk7 as a promising oncolytic viro-immunotherapy treatment for advanced OVCA and support its advancement toward clinical translation.
Safarnezhad Tameshkel F, Sadat Kalaki N, Karimi E
… +6 more, Razizadeh MH, Haidar AEH, Amiri A, Zaki M, Nikkhah M, Karbalaie Niya MH
Mol Ther Oncol
· 2026 Jun · PMID 42179967
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Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide; molecular biomarkers that reflect hepatitis B virus (HBV)/hepatitis C virus (HCV)-associated tumor biology and predict prognosis or therape...Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide; molecular biomarkers that reflect hepatitis B virus (HBV)/hepatitis C virus (HCV)-associated tumor biology and predict prognosis or therapeutic vulnerabilities are needed. The research is a secondary analysis of public data (secondary data analysis) based on Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) data to identify differentially expressed genes (DEGs) common to HBV-HCC, HCV-HCC, and non-viral HCC datasets. Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, protein-protein interaction (PPI) network analysis, and hub-gene selection were then performed. Differential expression, prognostic association, immune-infiltration, and drug-sensitivity correlations were also analyzed. Eighty common DEGs (73 upregulated, 7 downregulated) were identified. PPI topological analysis yielded 53 hub genes; five genes and , were prioritized and validated as significantly upregulated in liver HCC and associated with poorer overall survival. Immune deconvolution showed consistent positive correlations between the hub genes and B cells and regulatory T cell subsets, and negative correlations with mucosal-associated invariant T (MAIT) cells, macrophages, and natural killer (NK)/monocyte signatures. Drug-gene correlation analysis revealed positive associations of and with sensitivity to mitogen-activated protein kinase inhibitors and negative correlations with several targeted inhibitors. The identified prognostically unfavorable hub genes in HBV/HCV-associated HCC are associated with an immunosuppressive microenvironment and with patterns of drug sensitivity.
Alipourfard I, Shafaghat Z, Saharkhiz S
… +2 more, Farani MR, Bakhtiyari S
Curr Treat Options Oncol
· 2026 May · PMID 42176091
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Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment outcomes of patients with hematologic malignancies, including B-cell acute lymphoblastic leukemia (B-ALL), diffuse large B-cell lymphoma (...Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment outcomes of patients with hematologic malignancies, including B-cell acute lymphoblastic leukemia (B-ALL), diffuse large B-cell lymphoma (DLBCL), and multiple myeloma (MM). However, issues such as antigen escape, T-cell exhaustion, and the limited efficacy of CAR-T cells in acute myeloid leukemia (AML) and T-cell leukemias still persist. This review aims to summarize human trials and achievements from 2015 with a focus on the innovations within the last two years. We discuss strategies to overcome resistance, including multi-target CARs, next-generation constructs, and combination strategies to treat resistant cancers. We also explore the ways to increase safety and access, including allogeneic CAR-T options. In this article, we propose CRISPR-enhanced CARs and synthetic biology-based allogeneic systems to enhance the efficacy and accessibility of CAR-T therapy with the aim of moving the field of oncology towards durable cures.
Immune checkpoint inhibitors have reshaped the therapeutic landscape of hepatocellular carcinoma by restoring T cell-mediated antitumor immunity. However, the clinical benefit of monotherapy remains limited, highlighting...Immune checkpoint inhibitors have reshaped the therapeutic landscape of hepatocellular carcinoma by restoring T cell-mediated antitumor immunity. However, the clinical benefit of monotherapy remains limited, highlighting the need for improved patient stratification and more effective treatment strategies. HBV-related hepatocellular carcinoma (HBV-HCC) is a major etiological subtype characterized by a chronically immunosuppressive tumor microenvironment driven by persistent viral antigen exposure and immune exhaustion. We believe that patients with HBV-HCC may be more suitable for immunotherapy, especially treatment with immune checkpoint inhibitors. A deeper understanding of the expression patterns of inhibitory checkpoint and costimulatory molecules, along with the identification of predictive biomarkers and the development of effective combination immunotherapies is essential for improving clinical outcomes. From a safety perspective, hepatitis B virus reactivation is generally manageable when appropriate antiviral therapy is administered concurrently with immunotherapy. Consequently, patients with HBV-HCC should not be excluded from treatment with immune checkpoint inhibitors. We anticipate that combination strategies, including multi-target immune checkpoint blockade, combinations with other immunotherapeutic approaches, and microbiome-based therapy, will further enhance therapeutic efficacy in HBV-HCC. Combination immune checkpoint therapy may enhance antitumor responses and potentially contribute to better control of viral activity.