Afatinib, an irreversible ErbB family inhibitor, is approved for the treatment of non-small cell lung cancer (NSCLC) with both common and selected uncommon EGFR mutations. Evidence in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD) is scarce, especially with pharmacokinetic (PK) data. Here, we report the case of a patient with metastatic NSCLC harboring an EGFR G719C mutation who was successfully treated with afatinib during regular hemodialysis. Afatinib was initiated at 20 mg once daily under fasting conditions and later escalated to 30 mg once daily. PK sampling was conducted on two consecutive HD days at each dose level. At 20 mg, the trough concentration (Ctrough) was 4.02 ng/mL, with peak concentrations (Cmax) of 6.09 and 8.75 ng/mL, both lower than reported values in patients with normal renal function. At 30 mg, Ctrough increased to 26.3 ng/mL, while Cmax values of 48.2 and 55.5 ng/mL were comparable to steady-state exposures in patients with preserved renal function. Notably, no adverse events were observed, and the patient has maintained a partial response for over eight months. This case suggests that afatinib can be administered without major dose modification in HD patients, with PK data indicating minimal impact of dialysis and underscoring the importance of accumulating real-world evidence in this underrepresented population.

"Lineage switch" is a term used to describe the phenomenon of change of lineage of acute leukemia to a different lineage. It is typically seen during therapy or at the time of relapse. More commonly, it is described in the pediatric population with an incidence of 6-9%. Lineage switches, though uncommon, can occur from acute myeloid leukemia (AML) to acute lymphoblastic leukemia (ALL (B/T)) and vice versa. The present scenario of AML to B-ALL switch is rare in an adult, with only a handful of cases described in literature. We report herein a case diagnosed as AML at 56 years of age, with NPM mutation who relapsed after 18 months post initial diagnosis. The clinicopathological features, flowcytometry, and molecular characteristics are discussed.

Myeloid sarcoma (MS) refers to an extramedullary collection of immature cells of granulocytic series and occurs either in isolation or in association with myeloid malignancies, particularly acute myeloid leukemia (AML). We report a 16-year old girl with AML who was treated at our hospital with standard "7 + 3" induction chemotherapy and achieved morphological remission. She developed a small nodule below her right eyelid at day 10 of first consolidation chemotherapy with high-dose cytarabine. Eyelid lesion increased in size despite oral antibiotics. Peripheral blood did not show any blasts. However, bone marrow examination was consistent with relapsed AML. She was treated with salvage chemotherapy followed by allogeneic stem cell transplant. However, her disease relapsed 2 months later and she died. This is the first case of eyelid MS from India in which eyelid MS developed during chemotherapy for AML and heralded the subsequent disease relapse. Eyelid MS could be a sinister manifestation of AML. Literature regarding eyelid MS is discussed in brief.

Succinate dehydrogenase (SDH) deficient gastrointestinal stromal tumor (GIST) is the most common type of wild type GIST characterized by lack of mutations in proto-oncogene receptor tyrosine kinase (KIT) or platelet-derived growth factor receptor alpha (PDFGR alpha) pathways. It has a unique predilection for females and young adults, with a relatively indolent prognosis and varied treatment modalities. Data regarding SDH GIST from the Indian subcontinent is sparse.

Liver metastasis continues to be a leading cause of cancer-related mortality, particularly in colorectal, pancreatic, and breast cancer. The successful establishment of metastatic lesions depends critically on the liver metastatic tumor microenvironment, where reciprocal cellular interactions between disseminated tumor cells and both parenchymal hepatocytes and non-parenchymal cells facilitate tumor cell colonization and outgrowth. Hepatic macrophages that encompass both tissue-resident Kupffer cells (KCs) and monocyte-derived macrophages (Mo-Macs) have emerged as pivotal regulators of liver metastatic progression. This review summarizes recent progress from the following perspectives: (I) Primary tumors recruit macrophages via secretion of cytokines and exosomes, or induce phenotypic alterations in resident KCs and recruited Mo-Macs, thereby establishing a premetastatic niche; (II) Once the premetastatic niche is formed, hepatic macrophages directly interact with tumor cells to mediate their capture, colonization, and subsequent outgrowth; (III) Furthermore, hepatic macrophages regulate phenotypic changes in T cells, NK cells, hepatocytes, and hepatic stellate cells (HSCs) through cytokine/exosome secretion or direct cell-cell interactions, which induce T cell exhaustion, impairment of NK cell cytotoxicity, and activation of HSCs leading to fibrotic microenvironment formation. Additionally, we review advances in macrophage-targeted therapeutic strategies against liver metastasis. By delineating the pivotal roles of hepatic macrophages in metastatic progression and analyzing current clinical limitations of targeting macrophages for liver metastasis therapies, this review provides foundational insights for understanding macrophage biology and developing effective therapeutics.

Chronic obstructive pulmonary disease (COPD) and lung cancer are highly correlated and frequently co-occur. Any degree of COPD significantly increases the risk of developing lung cancer, suggesting they may share common pathogenic mechanisms. The hypoxia-inducible factor 1 (HIF-1) signaling pathway, a complex regulatory network for cellular sensing and response to hypoxia, is abnormally activated in both COPD and lung cancer. Chronic inflammation, immune microenvironment imbalance, extracellular matrix remodeling, epithelial-mesenchymal transition, angiogenesis, and epithelial differentiation, all closely related to the HIF-1 pathway, lie at the intersection of both diseases. Consequently, the HIF-1 pathway is proposed as a potential molecular mechanism underpinning the occurrence, progression, and poor prognosis of lung cancer with COPD (LC-COPD). In this review, we focus on the role and mechanisms of HIF-1 in advancing LC-COPD, highlighting its promising potential as a therapeutic target.

myxoinflammatory fibroblastic sarcoma is a rare type of sarcoma characterized by the abnormal growth of mesenchymal tissue. It is known for its locally aggressive behavior, high recurrence rate, and potential for metastasis. Clinically, it typically presents as a superficial, painless subcutaneous mass, although it may sometimes cause pain and restricted movement. Histologically, comprises spindle cells with myxoid stroma and large atypical cells with marked nuclear pleomorphism, similar to Reed-Sternberg cells.

Von Hippel-Lindau (VHL) disease is a rare inherited tumor syndrome characterized by the development of multiple neoplasms. The broad variability in clinical manifestations makes this entity susceptible to being overlooked during clinicpathological diagnosis. A female patient in her late 20s presented with multiple adrenal masses during a routine health check-up, with associated dizziness and palpitations lasting 1 month. Laboratory studies revealed plasma-free normetanephrine level of 2894.9 pg/ml. Abdominal contrast-enhanced computed tomography showed multiple lesions consisting of bilateral adrenal masses and retroperitoneal nodules. Postoperative pathological examination demonstrated the diagnosis of bilateral adrenal pheochromocytomas, retroperitoneal paraganglioma, and pancreatic neuroendocrine tumor. Molecular genetic testing detected a pathogenic germline mutation in the VHL gene (c.499C > T: p.R167 W). Subsequent brain magnetic resonance imaging revealed a hypervascular cerebellar nodule. Genetic and clinical findings confirmed a definitive diagnosis of VHL syndrome type 2B. The diverse manifestations of VHL syndrome often cause diagnostic delays. Analyzing this case alongside the literature highlights the need to suspect VHL in young patients with multiple tumors, for whom genetic testing is crucial for definitive diagnosis. While a single case cannot capture the full disease spectrum, it provides valuable clinical insight.

Atypical breast lesions are high-risk findings found on some core needle biopsies that may represent concurrent malignancy. Clinical management remains uncertain due to wide variability in reported upgrade rates and an incomplete understanding of contributing risk factors. Risk prediction models have been developed to estimate likelihood of malignant upgrade (from atypia to malignancy), but these models are highly variable in performance and predictor selection. This systematic review evaluates existing models predicting upgrade to malignancy in high-risk breast lesions, focusing on clinical applicability.

The transient receptor potential melastatin (TRPM) family consists of eight members (TRPM1-8), which play a pivotal role in regulating cation fluxes, including K+, Na+, Ca2+, and Mg2+. While these channels are integral to various physiological functions, emerging evidence links TRPM dysregulation to the pathogenesis of colorectal cancer (CRC), one of the most prevalent and deadly malignancies worldwide. This review highlights the multifaceted roles of TRPM channels in CRC pathogenesis, their potential as diagnostic and prognostic biomarkers, and their therapeutic applications. Recent research has revealed that certain types of TRPM channels and specific noncoding RNAs within TRPM loci are implicated in critical oncogenic processes such as proliferation, migration, invasion, and epithelial-mesenchymal transition. Specific members, including TRPM4, TRPM7, and TRPM8, exhibit diverse effects in CRC, ranging from modulating metastasis to influencing chemoresistance. Despite their significant role in CRC, conflicting findings on TRPM expression levels in patient tissues highlight the complexity of their involvement and necessitate further research. TRPM modulators show therapeutic potential as anticancer agents. However, challenges in specificity and off-target effects currently limit their clinical application. Advancing our understanding of TRPM function in CRC could hold promise for novel treatment strategies to improve patient outcomes.

Circulating tumor DNA (ctDNA) enables early detection of ESR1 mutations in hormone receptor-positive, HER2-negative metastatic breast cancer. Building on the PADA-1, the SERENA-6 trial demonstrated significant progression-free survival and quality-of-life benefits from ctDNA-guided early endocrine switching before radiologic progression.

Antibody-drug conjugates (ADCs) have demonstrated promising efficacy in several prospective clinical studies, offering new possibilities for the treatment of non-small cell lung cancer (NSCLC). Consequently, understanding the toxicity profile associated with ADCs is of critical importance.

Non‑small cell lung cancer (NSCLC), accounting for >85% of LC cases, remains a therapeutic challenge due to its low 5‑year survival rate, tumor heterogeneity and drug resistance. The SRY‑related high‑mobility group‑box (SOX) family comprises transcription factors involved in the initiation and progression of NSCLC. These factors regulate epithelial‑mesenchymal transition and angiogenesis, interact with epidermal growth factor receptor/KRAS pathways to influence tumor invasion and promote chemotherapy resistance by sustaining tumor stemness. The present review aimed to summarize the expression patterns, molecular mechanisms and clinical relevance of SOX family members (such as SOX2, SOX4 and SOX9) in NSCLC, as well as their potential as diagnostic biomarkers and therapeutic targets, and the application of emerging technology in elucidating their functions. The present review aimed to provide a theoretical foundation for precision diagnostics and therapeutics to foster more effective NSCLC treatment.

Effective anti-tumor immunity critically depends on functional CD8+ T cells, yet in almost all solid tumors, these cells become dysfunctional, exhausted, or spatially excluded. This breakdown of immune surveillance arises not only from cell-intrinsic T cell exhaustion but also from multimodal communication among tumor, stromal, and immune cells within the tumor microenvironment (TME). This communication is mediated not only through direct receptor-ligand interactions but also through a suite of indirect mechanisms, such as metabolic competition, secretion of immunosuppressive metabolites and cytokines, extracellular vesicle exchange, and even mitochondrial transfer via tunneling nanotubes or membrane transfer through T cell trogocytosis. Together, these suppressive interactions impair CD8+ T cell metabolism, effector function, and persistence, thereby enabling tumor immune evasion. In this review, we summarize current understanding of how multimodal cell-cell communication, including immune checkpoints, metabolic reprogramming, and stromal crosstalk, cooperatively drive CD8+ T cell dysfunction. We also highlight emerging therapeutic strategies aimed at rewiring these suppressive networks, with emphasis on translational potential. A deeper understanding of the spatial, molecular, and metabolic context of CD8+ T cell suppression offers new avenues to enhance the efficacy of cancer immunotherapies.

Small cell lung cancer (SCLC) is challenging to manage due to its high malignancy and early metastatic spread. Although initial chemoradiotherapy responses are common, resistance rapidly develops, and long-term efficacy remains limited. Immune checkpoint inhibitors (ICIs) overcome previous survival barriers, extending overall survival (OS) and progression-free survival (PFS) in extensive-stage SCLC. Nevertheless, absolute clinical benefits remain modest. To address efficacy limitations, current research focuses on optimizing first-line strategies by exploring multimodal regimens (e.g., adding targeted therapy or radiotherapy to chemoimmunotherapy) and advancing molecular subtyping for precision oncology. Furthermore, emerging therapies such as DLL3-targeted agents, bispecific antibodies (bsAbs), antibody-drug conjugates (ADCs), and chimeric antigen receptor T-cell (CAR-T) therapy continue to demonstrate clinical progress. This review synthesizes advances in SCLC management, focusing on mechanisms and clinical applications of multimodal strategies and novel therapies. It provides guidance for clinical decisions, research directions, and survival improvement.

Bone metastases (BM) are a frequent and clinically relevant manifestation in patients with metastatic pheochromocytomas and paragangliomas (mPPGL).

Follicular dendritic cell sarcoma (FDCS) is an uncommon malignant neoplasm that arises from follicular dendritic cells (FDCs). The mediastinum is a more unusual site of FDCS. In this document, we detail a case involving the complete surgical removal of FDCS located in the mediastinum. A 28-year-old woman presented with symptoms of right chest pain. Accompanying symptoms include chest tightness, shortness of breath, and faintness. Chest computed tomography was performed and revealed abnormal enhancement in the mediastinal region. An excisional biopsy was carried out, and through the aid of immunohistochemistry (IHC), a diagnosis of FDCS was confirmed. Following surgery, the patient underwent radiotherapy for 27 sessions. The patient was followed up by the oncology service for 6 years and was still alive at the time of drafting this report. This exceedingly uncommon case underscores the challenges in making a differential diagnosis and emphasizes the significance of diagnostic indicators, including histopathology and IHC, in establishing a diagnosis. Clinicians should be alert to the possibility of encountering this disease and take into consideration various characteristics to avoid misdiagnosis.

Cell death is a fundamental process essential to all living organisms, with apoptosis serving as one of the most crucial pathways across various stages of life. Dysregulation of apoptosis is closely associated with numerous diseases, particularly cancer. PUMA (p53 upregulated modulator of apoptosis) is a key mediator of apoptotic cell death. It is activated in response to a wide range of internal and external signals. Beyond its established role in apoptosis, PUMA also regulates other forms of cell death, including necroptosis, autophagy, and ferroptosis, underscoring its critical role in cancer cell death, especially during chemotherapy. However, PUMA activation is frequently impaired in many cancers, leading to resistance to cell death and treatment failure. This review highlights recent advancements in understanding the regulation of PUMA expression at multiple levels, including epigenetic, transcriptional, post-transcriptional, and post-translational mechanisms. It also examines the influence of diverse cellular regulators, such as epigenetic modifiers, transcription factors, non-coding RNAs, kinases, and ubiquitin ligases in modulating PUMA activity. Additionally, we discuss PUMA's role in cancer progression, its impact on the effectiveness of anti-cancer therapies, and its potential as a prognostic biomarker for therapeutic resistance. Finally, we propose critical questions to inspire future research, aiming to deepen the understanding of PUMA regulation and its significance in cancer therapy.

Cancer causes dysregulation of apoptosis, a genetically controlled mechanism necessary for growth and homeostasis, which permits unchecked cell division and resistance to cell death. The Warburg effect, metabolic flexibility, and glucose reliance of malignant cells are highlighted in this chapter's analysis of the molecular interactions among insulin/IGF-1 signaling, carbohydrate metabolism, and tumor biology. We examine the data relating increased tumor survival, proliferation, and metastasis to hyperglycemia, hyperinsulinemia, and inflammatory cytokines. In the context of primary, secondary, and tertiary cancer prevention across a variety of tumor types, including colorectal, prostate, breast, and head and neck cancers, the epidemiological and experimental literature on dietary carbohydrates-from simple sugars to complex fibers-is assessed. There is discussion of mechanistic processes involving altered metabolism, hormonal regulation, and acidity of the microenvironment. While recognizing discrepancies and data gaps that need more study, the chapter emphasizes dietary modification-specifically, limiting carbohydrates and increasing fiber intake-as a promising adjunct in cancer prevention and survivorship.

Active surveillance (AS), first described as a management strategy for favorable risk prostate cancer more than 20 years ago has now been widely adopted as the treatment of choice for these patients. AS surveillance initially consisted of regular PSA monitoring with periodic biopsies, with intervention indicated for rapid rise in PSA or upgrading. Novel tools in the AS pathway and a deeper understanding of the biology of prostate malignancies have allowed the approach to be considerably refined.