Although immune checkpoint inhibitors (ICIs) and targeted therapies (TTs) have transformed the treatment of non-small cell lung cancer (NSCLC) across disease stages, real-world access remains highly unequal worldwide. Persistent cost barriers, fragmented reimbursement frameworks, and heterogeneous regulatory pathways limit equitable availability. The rapid proliferation of me-too agents has been proposed to counter monopolies; yet, this expansion has not consistently improved affordability. Heterogeneous evidentiary requirements-along with differences in clinical end points, comparator selection, crossover policies, and treatment duration-fragment therapeutic markets and complicate assessment of incremental clinical benefit. Divergent regulatory decisions, particularly between the US Food and Drug Administration and European Medicines Agency, underscore how trial design and geographic representation influence drug availability, especially when approvals rely on single-country data sets. These challenges are amplified in perioperative treatment strategies and rare oncogene-defined subgroups, where feasibility constraints and limited clinical equipoise hinder large randomized trials. As a result, an increasingly crowded therapeutic landscape makes cross-trial comparisons difficult and allows disparities in patient access to persist despite multiple approved therapies. Dose selection has historically followed maximum tolerated dose principles, even when preclinical and pharmacologic data suggest activity plateaus at lower exposure of ICI and TT. Dose and schedule optimization-through reduced dosing, extended intervals, or other deintensified strategies-therefore represents a rational and ethically grounded approach with a meaningful clinical impact. Such strategies may preserve efficacy while improving tolerability, reducing treatment burden, and mitigating financial toxicity, particularly in resource-limited settings. Aligning regulatory frameworks with dose optimization could promote more scalable, equitable, and sustainable NSCLC innovation.

Despite the availability of several chemotherapeutic regimens for early-stage breast cancer (BC), the ideal combination and dosing strategy remain to be defined. Thus, we conducted a network meta-analysis (NMA) comparing the current chemotherapeutic regimens used in the treatment of women with early-stage BC.

Diabetes mellitus and cancer are growing global health concerns with a rising prevalence and substantial associated mortality. The study aims to find impact of diabetes mellitus in cancer. A narrative review was conducted by analysing evidence from various sources, including meta-analyses, systematic reviews, retrospective studies, database analyses, and cohort studies. The review explored the complex interplay between Diabetes Mellitus and cancer, like cancer incidence, oncology outcome i.e., acute and late toxicities, treatment compliance, overall survival (OS), and quality of life (QoL). Diabetes mellitus increases the risk of developing cancer by 10%. Diabetic patients had higher infection rates [2.6%-52%, odds ratio (OR) 1.38-1.57], increased haematologic toxicity (13%-65.7%, P=0.004), and greater hospital admissions (17.2%-74.5%, OR 2.1, P< 0.001). They received significantly lower cisplatin doses (18%-33% reduction), experienced more surgical delays [adjusted OR 1.16, 95% confidence interval (CI) 1.05-1.27], higher risk of flap failure (RR=1.83, 95% CI 1.18-2.85, P=0.007) and were less likely to undergo breast reconstruction (adjusted OR 0.48-0.54, 95% CI 0.24-1.00). Diabetes mellitus decreases local control by 10-20%, increases mortality by 27-98%, and decreases OS by 18-50% across various cancers. It increases late toxicity and negatively impacts QOL with a 1.3-2.7 times higher risk of grade ≥2 genitourinary and gastrointestinal toxicity in prostate cancer, a twofold increase in grade ≥3 radiation pneumonitis in lung cancer, and a 50% higher incidence of severe peripheral neuropathy in breast cancer, leading to delayed recovery and long-term morbidity. In patients receiving cancer directed therapy, diabetes mellitus increases acute and late toxicities, decreased local control and overall survival, and have poor quality of life.

Cancer therapy imposes sustained mechanical and biochemical stress on lymphatic tissues, reshaping the signaling environments in which endothelial and contractile programs operate via molecular signals, cell-cell interactions, and mechanical forces. We propose that cancer-associated lymphedema arises from destabilized receptor crosstalk within integrated lymphatic signaling units rather than solely from anatomical insufficiency. Lymphatic vessels function as multicellular signal-processing systems in which receptor activity is context dependent and continuously modulated by ligand availability, tissue stiffness, inflammatory tone, and metabolic state. Under therapeutic stress, receptor systems that are secondary under homeostatic conditions, including mechanosensitive ion channels, purinergic receptors, and stress-responsive G protein-coupled receptors, can exert disproportionate influence over endothelial transcription, barrier function, contractile coordination, and immune-vascular feedback loops. Sustained activation of these networks may reinforce inflammatory and remodeling programs, providing a mechanistic explanation for delayed onset, nonlinear progression, and interindividual variability. This signaling-centered framework positions lymphatic failure after cancer therapy as a disorder of network integration and identifies stress-responsive receptor systems as tractable points for early intervention.

Neuropilin-1 (NRP1) is overexpressed in various malignant solid tumors, modulating the tumor microenvironment (TME) via multiple mechanisms to promote immune suppression, angiogenesis, and epithelial-mesenchymal transition (EMT), ultimately resulting in poor patient survival. Autophagy, a highly conserved cellular self-degradation process, plays a stage-dependent, bidirectional role in cancer. At early stages it suppresses tumorigenesis by clearing damaged cellular components, whereas at advanced stages it supports tumor survival under stress and thereby enhances proliferation, invasiveness, and therapy resistance. The interplay between NRP1 and autophagy in the TME is characterized by reciprocal regulation: NRP1 activates certain pathways to regulate autophagy, whereas autophagy induction promotes NRP1 degradation. This bidirectional interplay directly governs tumor progression and therapy resistance. Although prior studies have provided some clues about their interaction, the regulatory network and the precise mechanisms linking NRP1 and autophagy in the TME remain incompletely characterized. Precision therapies targeting the NRP1-autophagy axis still face multiple obstacles. This review synthesizes data from the atlas cancer genome (TCGA), the genotype-tissue expression (GTEx) database, and the human autophagy database (HADb) to explore associations between NRP1 and autophagy-related gene (ATG) in expression and prognosis, elucidate NRP1-autophagy interaction mechanisms and therapeutic opportunities and challenges in targeting the NRP1-autophagy axis. Pan-cancer analysis showed significant upregulation of NRP1 in 10 solid tumor types and revealed co-expression relationships between NRP1 and 340 ATGs. Among these, co-expression patterns involving genes such as CXCR4 and HSPA5 had significant prognostic value in gastric cancer and glioblastoma. This review systematically explores the panoramic regulatory framework of the NRP1-autophagy axis in the tumor immune microenvironment through bidirectional regulation of activating immunity and inhibitory immunity at the pan-cancer level. It fills the gap in the systematic summary of the NRP1-autophagy axis in regulating the dynamics of the tumor immune microenvironment, and provides a theoretical basis for the clinical translation of combination chemotherapy and immunotherapy targeting the NRP1-autophagy axis.

Therapeutic resistance remains the principal cause of mortality in breast cancer. While the tumor microenvironment (TME) is a key contributor, therapies targeting isolated TME components, whether immune, metabolic, or spatial, have largely failed due to compensatory adaptations and ecological resilience. This review synthesizes recent advances to propose a tripartite "Immune-Metabolic-Spatial" axis as the fundamental organizer of a robust resistance niche. We elucidate how immunosuppressive cells, such as TAMs and Tregs, are metabolically sustained by altered nutrient availability like lactate and hypoxia, while spatial constraints, including CAF-deposited ECM and DDR1-mediated collagen alignment, physically impede drug delivery and immune infiltration. Critically, we highlight reciprocal crosstalk where metabolic reprogramming dictates immune cell function, in turn influencing stromal remodeling to create a self-reinforcing resistance loop. Beyond mechanism, we evaluate emerging strategies that concurrently target multiple axes, such as combining immune checkpoint blockade with metabolic inhibitors or stromal disruptors. Finally, we discuss clinical translation through biomarker development and innovative trial designs, framing the tripartite axis as an actionable framework for overcoming therapeutic resistance.

Epithelioid angiosarcoma (EA) is a malignant tumor of endothelium origin that most commonly arises in the deep soft tissues of extremities but may occasionally be primary in skin, adrenal gland, and bone. A 72-year-old male presented with a painless enlargement of his thyroid for more than 10 days before hospitalization. A walnut-sized mass in the right thyroid was found simultaneously by palpation and Color Doppler Ultrasound. After a total thyroidectomy was performed, a mass with a size of 4.5 cm × 3.5 cm was found at the lower pole of the right thyroid gland. Histologically, the tumor was diffusely distributed in a sheet-like pattern, with tumor cells being epithelioid. There was extensive coagulative necrosis while no components of papillary carcinoma, follicular carcinoma and insular poorly differentiated carcinoma were noticed. CD31 and vimentin were positive for immunostaining. The diagnosis of primary epithelioid angiosarcoma of right thyroid was then given to the patient. Eleven months after the operation, the patient died from brain metastasis. It is suggested that primary epithelioid angiosarcoma of thyroid, as an extremely rare tumor, have no characteristic clinical manifestations, laboratory and imaging examinations, and the diagnosis mainly depend on its unique clinical pathological features. Although extensive surgical resection is the preferred treatment, the prognosis is still very poor.

Angiogenesis, which is the formation of new blood vessels from existing vasculature, exhibits a pivotal role in breast cancer progression and promotes metastasis. This complex biological process is influenced by the dynamic balance of pro- and anti-angiogenic factors within the tumor microenvironment, such as vascular endothelial growth factor, fibroblast growth factors, and angiopoietins. Targeted therapeutic strategies have been developed to interfere with angiogenic signaling, aiming to normalize or inhibit the tumor vasculature. In recent years, miRNAs have arisen as crucial post-transcriptional regulators of gene expression implicated in angiogenic homeostasis. These microRNAs can function as either promoters or suppressors of angiogenesis by targeting mRNAs that encode angiogenic factors or other signaling molecules. Deregulated expressions of these miRNAs in BC are associated with perturbed angiogenesis, tumor progression, and therapeutic resistance. This review presents a thorough overview of the molecular processes controlling angiogenesis in BC and highlights the emerging roles of angioregulatory miRNAs. The article also discusses the therapeutic potential of targeting miRNAs to modulate tumor angiogenesis, providing novel insights for the development of miRNA-based diagnostics and therapeutics in BC management.

Globally, hepatocellular carcinoma (HCC) ranks as the third most common cause of cancer-related death. The five-year overall survival (OS) rate for patients with unresectable HCC is only 12%. Currently, systemic therapies have become the primary treatment options for unresectable hepatocellular carcinoma. Studies comparing the efficacy of first-line treatments including lenvatinib, atezolizumab plus bevacizumab, and sorafenib have shown inconsistent results. There remains a need for updated comparative evidence on cross-mechanism therapy regimens for unresectable disease, as existing findings are still not completely clear. This network meta-analysis aims to provide clearer insights into which treatment offers greater efficacy for patients with unresectable HCC.

Tumor budding (TB) has been recommended as a marker for prognosis and therapeutic decision-making in various types of cancer, yet it has not been comprehensively studied in gynecological malignancies. This study aimed to evaluate the relationship between TB and clinicopathological features, as well as prognosis, in patients with gynecological malignancies, using a Bayesian meta-analysis design.

Tumor lysis syndrome (TLS) in patients with lung cancer (LC) is poorly characterized, due to its predominance in hematologic malignancies, creating a gap in both recognition and management strategies.

This meta-analysis aims to evaluate the diagnostic efficacy of [68Ga]Ga-FAPI PET imaging in breast, ovarian, and cervical cancers by conducting a systematic review of the existing literature.

Invasive lobular carcinoma (ILC) represents the most common special subtype of breast cancer. Studies show challenges with imaging, surgical therapy, and systemic therapy selection, arguing for the need for improved treatment personalization for this histologic subtype of breast cancer. While standard imaging tools have decreased sensitivity for ILC, newer imaging approaches may be more effective in both early and advanced disease settings. Surgical treatment is notable for high rate of positive margins and need for more extensive surgery; this may be mitigated by improved imaging and incorporation of particular techniques. While endocrine therapy remains the mainstay of treatment for most patients with ILC, the unique molecular characteristics of this tumor type may provide targets for new therapeutic approaches. The preponderance of data supports the need for ILC specific studies and trials.

IgD multiple myeloma is an exceptionally rare subtype, accounting for less than 2% of all multiple myeloma cases.

Beta-human chorionic gonadotropin (β-hCG) is commonly used in pregnancy detection and as a tumor marker for reproductive system cancers.

Brain metastases arise from the spread of cancer cells from tumors residing outside the brain. Immunotherapy and molecularly targeted therapeutics have improved outcomes for some patients with brain metastases, but many patients are still faced with a dismal prognosis. The inability to effectively treat these tumors and improve patient survival highlights the dire need for improved therapeutic strategies that ultimately depend on developing a greater understanding of the molecular underpinnings and inner wiring of these tumors. In this Review, we discuss current and emerging insights into the genetics and cellular signaling pathways that contribute to the spread of tumors to the brain. We also discuss potential therapeutic targets in the metabolic vulnerabilities of cells that metastasize to the brain and in the interactions between metastases and the microenvironment.

Mucosal melanoma (MM) represents a rare malignancy in Caucasian populations but constitutes one of the predominant melanoma subtypes among non-Caucasian ethnic groups. Due to its anatomic occult nature, a significant proportion of patients with MM present with advanced-stage disease at diagnosis. Characterized by distinct genomic profiles and an immunosuppressive tumor microenvironment, MM exhibits suboptimal responses to current targeted drugs and immune checkpoint inhibitors (ICIs). Combination immunotherapy can overcome immune evasion by enhancing the infiltration of tumor-specific antigen-reactive T lymphocytes, thereby exhibiting potentiated anti-tumor activity. However, the rarity of MM has posed significant barriers to better understanding immunotherapy resistance mechanisms and investigating novel therapies. Consequently, there is a critical unmet need for establishing standardized treatment guidelines to improve survival outcomes in advanced MM. This article comprehensively reviews current status in the treatment of advanced MM. It also discusses potential future directions for treatment based on recent advances from clinical trials and basic research.

Cuproptosis is a regulated, copper-dependent form of cell death driven by mitochondrial protein lipoylation and disruption of the tricarboxylic acid (TCA) cycle. Increasing evidence in gynecologic oncology indicates that copper transport, lipoate metabolism, and respiratory-chain phosphorylation influence tumor fitness and treatment response. This review evaluates cuproptosis as a therapeutic hypothesis across gynaecologic cancers and outlines actionable targets and strategies based on this mechanism. Mechanistically, ferredoxin 1 (FDX1)-mediated lipoylation enables copper excess to precipitate TCA enzyme-dependent proteotoxic stress that is distinct from apoptosis and ferroptosis. Therapeutic concepts arising from this biology include modulation of copper flux with ionophores or chelators, inhibition of lipoic acid synthases, and disruption of mitochondrial proteostasis. Clinically, cuproptosis-related transcriptional signatures and imaging markers of mitochondrial respiration may help stratify patients for combination regimens that incorporate poly (ADP-ribose) polymerase inhibitors, anti-angiogenic agents, or immune checkpoint blockade. By synthesizing available mechanistic and translational evidence and highlighting trials-ready strategies, this review positions cuproptosis as a tractable, precision-oriented pathway for ovarian, cervical, and endometrial cancers.

The potential roles of chemical, physical, and viral factors in cancer development are well documented. Similarly, bacterial carcinogenesis has been reported previously, though not extensively. Therefore, we aimed to provide comprehensive, mechanistic evidence on the pathogenesis of bacteria-induced carcinogenesis and possible treatments to halt cancer progression. Infections by bacteria, including Salmonella typhi, Fusobacterium spp., Chlamydia pneumoniae, Staphylococcus aureus, Helicobacter pylori, and Mycobacterium tuberculosis, have been reported as the most common carcinogenic bacteria in humans. These bacteria can produce toxins and carcinogenic metabolites those promote the development of cancer in a variety of ways, including by changing the dynamics of the cell cycle, triggering signaling pathways in the cell, such as NF-κB, MAPK, PI3K-PKB/Akt, and JAK/STAT, and activating anti-apoptosis activities by increasing Bcl-2 and decreasing BAX, and caspases expression along with suppressing p53 and pRb tumor suppressor proteins. Moreover, inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interferon-gamma (INF-γ), interleukin-1β (IL-1β), IL-4, IL-6, IL-10, IL-1, IL-17, IL-23, and other inflammatory cytokines are a few of the factors that promote chronic inflammation and initiate carcinogenesis. In addition, bacterial infection can generate free radicals that induce DNA damage, thereby promoting carcinogenesis. Following these mechanisms, bacteria can cause a wide range of cancers, such as breast, colon, pancreas, stomach, lung, gallbladder, and oral carcinoma. Fortunately, supplementation with active natural phytochemicals and nano-based strategies may counteract bacterial infection-induced carcinogenesis by regulating several cellular proteins, including those that control the cell cycle, induce apoptosis, promote metastasis, interact with growth factor receptors and tyrosine kinases, and function as antioxidants. Therefore, this narrative review aims to provide a consolidated mechanistic overview of bacterial infection-induced carcinogenesis and to highlight emerging phytochemical and nanotechnology strategies as potential therapeutic approaches. Additionally, phytochemical-based interventions and nanotechnology strategies are discussed as potential alternative therapeutic approaches to counteract bacteria-induced carcinogenesis.

Pancreatic cancer is a very deadly disease, with no effective therapy currently employed in clinical practice, highlighting the urgent need for new therapeutic strategies. Cancer cells represent a minority within the pancreatic tumor, which is characterized by a pronounced stromal compartment. As fibrosis is characteristic of pancreatic ductal adenocarcinoma, the cell population of particular interest is the pancreatic cancer-associated myofibroblast population, observed to be the main extracellular matrix producers. Recent studies revealed a plurality of myofibroblast functions in the pancreatic tumor, beyond their role in matrix secretion: they were noted to promote cancer cell proliferation and invasiveness in in vitro and in vivo studies, and have been described as potential prognostic biomarkers, along with stromal collagen content. Moreover, myofibroblasts were found in precancerous pancreatic lesions, and may thus be involved in pancreatic carcinogenesis. Paradoxically, depletion of myofibroblasts had detrimental effects on the outcome in an in vivo study, and their precise role in the disease remains unclear. This review summarizes for the first time studies on pancreatic cancer-associated myofibroblasts, focusing on the origin, function, biomarker potential, and heterogeneity of these cells in the pancreatic tumor, aiming to elucidate their role in pancreatic cancer progression.