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Novel, tailored therapeutic regimens have revolutionized the treatment of hematologic malignancies. However, cardiotoxicity remains a potential barrier to effective treatment and an important clinical concern due to its diverse mechanisms and potential impact on patient outcomes. Breakpoint cluster region-Abelson (BCR-ABL) tyrosine kinase inhibitors and Bruton tyrosine kinase (BTK) inhibitors disrupt pro-survival molecular cascades or activate cell-death pathways through distinct on- and off-target mechanisms. Proteasome inhibitors induce excessive production of reactive oxygen and nitrogen species in myocardial and endothelial cells through the accumulation of misfolded or damaged proteins. Immunotherapies that deregulate cross-talk between immune and cardiovascular (CV) cells trigger systemic inflammatory responses, resulting in life-threatening CV adverse events. Unlike conventional chemotherapy, targeted therapies, immune checkpoint inhibitors, and cellular therapies induce CV complications through distinct pathways, including direct myocardial injury, immune-mediated inflammation, cytokine release, and endothelial dysfunction. These mechanisms result in a broad spectrum of CV toxicities, including heart failure, myocarditis, arrhythmias, and hypertension, which are characterized by early onset and variable reversibility. Recognizing mechanism-specific toxicity is essential for timely diagnosis, risk stratification, and tailored monitoring, including the use of cardiac biomarkers and advanced imaging techniques. Early detection may facilitate prompt intervention, minimize treatment interruptions, and improve both oncologic and CV outcomes. Consequently, integrating cardio-hemato-oncology into routine clinical care is vital and requires a multidisciplinary and individualized approach to optimize therapy, reduce morbidity, and enhance long-term survival in hematology patients receiving novel oncologic treatments. This review summarizes the molecular mechanisms linking novel hemato-oncology therapies to CV adverse events, providing current insights into clinical practice, monitoring, and management to help improve patient outcomes and guide future research.

Introduction: Melanoma exhibits substantial geographic heterogeneity in incidence, mortality, and subtype distribution. Independent population-based studies indicate that superficial spreading melanoma is more common in Oceania, whereas acral and mucosal melanomas constitute a larger proportion of melanoma in East and Southeast Asia, where epidemiological patterns differ substantially across countries and territories in the Western Pacific region. We aimed to characterize divergent melanoma incidence and mortality trajectories and quantify the demographic contributors to changes in absolute burden across the Western Pacific region from 1990 to 2021. Methods: Data from the Global Burden of Disease Study 2021 for 28 Western Pacific countries and territories within the WHO Western Pacific Region with complete GBD 2021 melanoma estimates were analyzed overall and stratified into an Oceania subregion (Australia and New Zealand) and an Asian-predominant subregion comprising the remaining included countries in East and Southeast Asia. Joinpoint regression was used to estimate annual percent changes (APCs) and average annual percent changes (AAPCs) with 95% confidence intervals (CIs); hierarchical clustering was used to group countries according to incidence-mortality trajectories; Das Gupta decomposition was used to quantify the contributions of population growth, aging, and epidemiological change to changes in absolute case and death counts; and Nordpred was used to generate conditional projections to 2045 with 95% prediction intervals (PIs). All rates were age-standardized to the Global Burden of Disease standard. Results: In Oceania, the population-weighted age-standardized incidence rate (ASIR) was 33.54 per 100,000 population, whereas age-standardized mortality rate (ASMR) declined (AAPC −1.28%, 95% CI: −1.70% to −0.86%). In the Asian-predominant subregion, the population-weighted ASIR was 0.58 per 100,000 population, but the ASMR increased (AAPC +0.39%, 95% CI: 0.36% to 0.42%). For incident cases, population growth and aging accounted for 53.9% and 34.1% of the net increase, respectively. For deaths, epidemiological change contributed −113.3% of the net increase, offsetting contributions from population growth and aging. The Republic of Korea had the largest increase in ASIR (AAPC 4.58%), whereas Australia had the largest decline in ASMR (AAPC −1.64%). By 2045, incident cases and deaths are projected to reach 201,744 (95% PI: 179,523 to 224,763) and 16,909 (95% PI: 14,357 to 19,868), respectively, under current trends. Conclusion: The melanoma burden in the Western Pacific region shows two divergent epidemiological trajectories that are consistent with differences in subtype distribution and health-system context. Oceania’s experience indicates that UV protection and early detection may reduce mortality, whereas rising mortality in Asia underscores the need for improved recognition of acral and mucosal lesions and subtype-specific strategies. These findings support sociodemographic index (SDI)-stratified approaches that incorporate subtype-specific considerations into melanoma prevention, diagnosis, and health-system planning.

The Dickkopf (DKK) proteins, particularly DKK1, along with their receptor cytoskeleton-associated protein 4 (CKAP4), play crucial roles in the pathogenesis and progression of gastrointestinal (GI) cancers. The DKK1-CKAP4 axis activates the phosphoinositide 3-kinase/ protein kinase B (PI3K–AKT) signaling pathway, thereby promoting the proliferation, migration, and invasion of cancer cells. Simultaneously, this axis modulates the tumor immune microenvironment (TME) by influencing the recruitment and activity of various immune cells, such as tumor-associated macrophages, regulatory T cells, and cytotoxic T cells. The co-expression of DKK1 and CKAP4 is associated with poor prognosis in several GI malignancies, including esophageal, gastric, pancreatic, colorectal, and liver cancers. Preclinical studies have demonstrated that targeting the DKK1-CKAP4 axis using humanized antibodies or small molecule inhibitors can inhibit tumor growth, enhance cytotoxic immune cell infiltration, and improve responses to chemotherapy and immunotherapy. Early clinical trials evaluating anti-DKK1 therapies have yielded mixed results; however, studies enriched with DKK1-high patients have demonstrated encouraging efficacy, underscoring the critical importance of biomarker-driven patient selection. DKK1 expression has also emerged as a potential predictive biomarker for response to these therapies. Further investigation into optimal combination regimens and patient selection strategies is warranted to fully harness the therapeutic potential of targeting the DKK1-CKAP4 axis in GI malignancies. Modulating this immunomodulatory pathway represents a promising approach to overcome immunosuppression, enhance the efficacy of current immunotherapies, and improve the outcomes of patients with GI cancers.

Cancer cells undergo metabolic reprogramming to support proliferation, survival, and adaptation to environmental stress. Among the nutrients that contribute to these processes, glutamine serves as a source of carbon and nitrogen for biosynthesis, energy production, redox regulation, and replenishment of tricarboxylic acid cycle intermediates. The mechanistic target of rapamycin complexes (mTORC1 and mTORC2) are regulators of cellular metabolism that integrate nutrient availability, growth factor signaling, and stress responses. Increasing evidence indicates that reciprocal interactions between mTOR signaling and glutamine metabolism may contribute to tumor progression and therapeutic adaptation. In this review, we examine the relationship between glutamine metabolism and mTOR signaling in cancer. We summarize current evidence supporting the role of mTORC1 in regulating glutamine uptake, utilization, anaplerosis, and biosynthetic metabolism, while highlighting that the contribution of mTORC2 to glutamine metabolism appears more indirect and remains less well defined. We further discuss the interaction of the mTORC-glutamine axis with oncogenic pathways, including MYC and phosphoinositide 3-kinase (PI3K)/ protein kinase B (AKT) signaling, as well as tumor suppressor pathways (e.g., p53), and its potential role in therapeutic resistance. Finally, we discuss three emerging translational dimensions associated with the mTORC-glutamine axis: intracellular adaptation through autophagy and redox regulation, tumor-immune metabolic interactions, and dynamic metabolic biomarkers that may influence therapeutic responses. These dimensions are presented as related but distinct phenomena rather than components of a unified mechanistic model. Collectively, the available evidence indicates that glutamine metabolism and mTOR signaling form a context-dependent regulatory network that supports metabolic flexibility in cancer cells. Tumors exhibiting strong coupling between glutamine utilization and mTOR activity are particularly promising candidates for metabolic intervention, yet substantial heterogeneity exists across tumor types and genetic backgrounds. Current findings further suggest that successful therapeutic targeting of the mTORC-glutamine axis will likely require biomarker-guided patient stratification and rational combination strategies designed to overcome adaptive metabolic rewiring and treatment resistance.

Host microRNA (miRNA) dysregulation has recently been identified as a key mechanism that facilitates the synergistic relationship between viral pathogens and cellular transformation in virus-associated cancer. Oncogenic viruses, such as hepatitis B virus (HBV), hepatitis C virus (HCV), human papillomavirus (HPV), Epstein–Barr virus (EBV; human herpesvirus 4), Kaposi sarcoma-associated herpesvirus (KSHV; human herpesvirus 8), and human T-lymphotropic virus type 1 (HTLV-1) dysregulate host miRNA expression through viral oncoproteins, epigenetic remodeling, inflammatory signaling, and non-coding RNA interactions. These dysregulated miRNAs are subsequently disseminated via exosome-mediated intercellular communication, promoting tumor progression and remodeling of the tumor microenvironment. These mechanisms result in the loss of tumor-suppressive miRNAs (e.g., miR-34a, let-7, and miR-122) and the upregulation of oncogenic miRNAs (e.g., miR-21, miR-155, and miR-221/222), thereby promoting hallmark cancer processes, including excessive proliferation, immune evasion, and therapy resistance. This dysregulation has significant translational implications. Circulating and exosomal miRNAs serve as non-invasive diagnostic and prognostic biomarkers, while recent advances in machine learning (ML) approaches enhance the utility of miRNA-based diagnostic panels, improving diagnostic precision and predictive performance. Systematic profiling of tissue-specific miRNA signatures aids in early detection and risk stratification. From a therapeutic perspective, strategies aimed at restoring miRNA homeostasis are being developed. Therapeutic strategies currently under preclinical and early clinical evaluation include miRNA mimics (e.g., MRX34), antisense oligonucleotides (antagomiRs) such as cobomarsen (anti-miR-155), small-molecule inhibitors targeting miRNA biogenesis pathways, and clustered regularly interspaced short palindromic repeats (CRISPRs)-based genome-editing technologies. Notably, the combination of these agents with established immunotherapeutic approaches holds potential for synergistic anticancer effects. Despite these advances, several challenges remain, particularly in terms of delivery precision, off-target effects, and viral-host miRNA cross-talk. Future progress depends on the integration of multi-omics data via ML, advancement of nanoparticle delivery systems, leveraging CRISPR-based tools for precise modulation, and development of combination therapies with immunotherapy. In this review, we present an integrated framework of the complex interactions between viral agents and host miRNA networks in viral oncology. By bridging molecular mechanisms with emerging diagnostic and therapeutic breakthroughs, we propose a unifying concept in which diverse oncoviruses converge on common regulatory pathways governing host miRNA dysregulation, despite context-dependent differences in individual miRNA expression patterns. This synthesis transforms fragmented evidence into a coherent strategy for next-generation diagnostics and precision-based therapy.

In critically ill cancer patients, autonomic nervous system (ANS) dysfunction may contribute to hemodynamic instability and organ dysfunction and may be exacerbated by malignancy-related injury and anticancer treatment. This narrative review summarizes conventional methods for assessing ANS function, including heart rate variability (HRV), blood pressure variability (BPV), baroreflex sensitivity (BRS), and cardiovascular autonomic reflex testing, together with emerging approaches such as high-resolution multimodal monitoring (MMM) and artificial intelligence (AI). Host-organ unregulated response (HOUR) framework is used to integrate interactions among autonomic, neuroendocrine, inflammatory, immune, coagulation, metabolic, bioenergetic,and microcirculatory dysregulation. Collectively, these approaches may facilitate real-time assessment of autonomic function and tissue perfusion, thereby supporting risk stratification and individualized management in critically ill cancer patients.

Chimeric antigen receptor T-cell (CAR-T) therapy is a significant breakthrough in oncology; however, its use is limited by a range of distinctive toxicities. Besides well-known acute adverse events (AEs) such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), clinical experience has revealed a series of low-incidence yet potentially severe and long-term safety concerns, including delayed or chronic toxicities. This review describes the spectrum of these low-incidence AEs affecting multiple organ systems, including CAR-T-associated hemophagocytic lymphohistiocytosis/macrophage activation syndrome, respiratory complications, neurological complications beyond ICANS, cardiovascular complications, coagulopathies, secondary malignancies, and rare AEs involving other systems. These toxicities can be classified based on mechanistic analysis into four categories: CRS-extension type, on-target/off-tumor type, immune exhaustion/secondary type, and therapy-related malignancy type. The underlying pathophysiology is multifaceted, involving systemic inflammation, on-target/off-tumor effects, profound immune dysregulation, and interactions with patient-specific factors including pre-existing comorbidities, prior treatments, and genetic predispositions. Management remains challenging due to a paucity of prospective studies, incomplete mechanistic understanding, and a lack of validated predictive biomarkers and standardized diagnostic or treatment protocols. Future studies should prioritize mechanistic research, prospective validation of predictive tools, development of preventive strategies, next-generation CAR engineering, and establishment of international registries for long-term surveillance. Increasing awareness, ongoing clinical vigilance, and personalized management strategies are essential to maximize the long-term benefits of CAR-T therapy while minimizing its risks.

The management of early-stage colorectal cancer (CRC) is undergoing a significant transformation, from traditional clinical and pathological staging to a dynamic, molecular signature-driven approach utilizing circulating tumor DNA (ctDNA). Postoperative detection of minimal residual disease (MRD) has emerged as a strong independent prognostic biomarker. It identifies patients at high risk of recurrence while reducing unnecessary exposure to adjuvant chemotherapy for those cured by surgery alone. However, this success reveals a critical therapeutic dilemma. Standard adjuvant chemotherapy has a limited ability to eliminate MRD. Consequently, the molecularly defined high-risk subgroup currently has no proven therapy that effectively eradicates MRD and improves survival. In this review, we synthesize emerging therapeutic strategies designed to address this unmet need. Wediscuss ongoing clinical trials investigating intensified cytotoxic regimens, MRD-guided targeted therapies, and novel immunotherapy combinations, especially for microsatellite-stable (MSS) disease. Furthermore, this review examines the role of ctDNA dynamics as a surrogate endpoint for regulatory drug approval, a crucial step in accelerating the development of these novel therapies. Finally, we address the real-world challenges of implementation, including access disparities, equity gaps, and standardized clinical algorithms. We highlight how emerging technologies and global collaborations may further refine MRD detection. The eradication of MRD represents the next frontier in curing CRC; however, this demands focused clinical research and validated surrogate endpoints to translate prognostic insights into tangible survival benefits.

Background Homoharringtonine (HHT) suppresses the expression of the CCAAT/enhancer-binding protein alpha (CEBPA). Our previous retrospective analysis indicated that favorable outcomes were observed in acute myeloid leukemia (AML) with double-mutated CEBPA (CEBPAdm) when patients received an HHT-based induction regimen. To confirm these observations, we performed a prospective multicenter, single-arm trial to assess the efficacy of homoharringtonine, daunorubicin, and cytarabine (HAD) induction regimen in patients with CEBPAdm AML. Methods This prospective multicenter single-arm trial enrolled patients with newly diagnosed CEBPAdm AML who received the HAD induction regimen between June 1, 2020, and October 1, 2023. Consolidation therapy comprised three cycles of high-dose cytarabine (HDAC). The trial was registered at ClinicalTrials.gov (NCT04415008). The primary outcomes were event-free survival (EFS) and relapse-free survival (RFS). Secondary endpoints included complete remission (CR) rate, 30-day mortality, and overall survival (OS). Survival outcomes were estimated using the Kaplan-Meier method and compared with the log-rank test. Results A total of 61 patients with newly diagnosed CEBPAdm AML (median age 40 years, interquartile range [IQR] 30–47 years) were enrolled. After one course of HAD induction, 57 patients (93.44%) achieved complete remission (CR), and the overall CR rate after one or two courses reached 95.08% (58/61). Among the 58 responders, 46 patients (79.31% [46/58]) achieved measurable residual disease (MRD) negativity after the first induction. The 30-day mortality rate was 3.28% (2/61). At a median follow-up of 31.97 months (IQR 21.27–37.77), the estimated 3-year EFS, RFS, and OS rates were 77.86%, 82.16%, and 87.27%, respectively. Exploratory subgroup analyses showed a numerical trend toward inferior RFS in patients with the co-occurring colony stimulating factor 3 receptor (CSF3R)T618I mutation (P = 0.064); however, given the small subgroup size, these findings are hypothesis-generating only and require validation in larger cohorts. Conclusions The HAD regimen demonstrated promising clinical activity and an acceptable safety profile in young adult patients with CEBPAdm AML, with 3-year EFS and RFS rates that met the predetermined objectives of 72% and 75%, respectively.