Neoplasia is increasingly common in senior pet rabbits, with cutaneous melanoma being a rare but aggressive type. Its characteristics in rabbits are not fully understood.

A 5-year-old rabbit initially presented with a cutaneous mass at the ear base. Despite surgical excision, it recurred rapidly with multiple facial/chest masses and pulmonary metastases, leading to euthanasia. Pathological evaluation confirmed malignant melanoma, revealing features such as high mitotic activity and lymphovascular invasion; immunohistochemistry provided the definitive diagnosis.

This case highlights the highly aggressive and metastatic nature of cutaneous melanoma in rabbits, often resulting in a poor prognosis. Clinicians should be aware of melanoma's aggressive potential in rabbits. Surgical intervention alone may prove inadequate, and current treatment options in rabbits are limited. In this case, surgical intervention was not effective, likely because micrometastasis was already present. Treatment options remain limited, and euthanasia is often required in metastatic cases.

Survivorship research has historically centered on individuals treated for early-stage cancers, often overlooking those living with advanced and metastatic disease. As therapeutic advances extend survival, the population of people living with incurable cancers is growing, presenting unique clinical and psychosocial challenges. This perspective provides insights into: (i) the experience of living with advanced cancer from the perspective of a survivor and caregiver; (ii) recent advances in this research area, and (iii) strategies to address ongoing gaps within two key areas: the converging fields of survivorship and palliative care research and supporting people living with advanced and metastatic cancers who are experiencing significant prognostic uncertainty. Overall, we contend that survivorship research for people living with advanced and metastatic cancers must explicitly extend beyond survival outcomes to address the lived realities of long-term treatment, symptom burden, and uncertainty. We highlight the need for integrated survivorship and palliative care models that support quality of life throughout the illness trajectory and for clinical and research strategies that help survivors and caregivers navigate ongoing prognostic uncertainty. Prioritizing these areas in research and care delivery will better align cancer care with patient-centered outcomes across the illness trajectory for people living with advanced and metastatic cancers.

Immune checkpoint inhibitors have revolutionized cancer therapy, and their unintended side effects relate largely to inducing autoimmunity; effects on vascular functions have only rarely been observed so far. In this issue of Cancer Discovery, a puzzling finding is reported that has divergent clinical implications: PD-1 inhibitors make cytotoxic T lymphocytes secrete a Wnt pathway suppressor to the blood that opens the blood-brain barrier, both allowing circulating tumor cells to enter the brain and a chemotherapeutic to better reach tumor cells in brain metastases. See related article by Deo et al., p. 976.

BCR-ABL1-negative myeloproliferative neoplasms (MPNs) often exhibit overlapping clinical and morphological features, making accurate subcategorization challenging. The h-MICL (CD371) antigen, selectively expressed on leukemic stem cells (LSCs) and absent on CD34⁺CD38^- cells in normal or regenerating marrow, represents a potential diagnostic and prognostic marker.

This study aimed to evaluate the diagnostic utility of circulating CD34⁺CD38^-h-MICL⁺ cells in subtyping BCR-ABL1-negative MPNs and to assess their correlation with the Dynamic International Prognostic Scoring System (DIPSS) score. Additionally, to identify a cut-off value of CD34⁺CD38^-h-MICL⁺ cells that can effectively differentiate PMF.

Fifty-four patients with BCR-ABL1-negative MPNs were prospectively enrolled at a tertiary care center in North India over 18 months. Peripheral blood was analyzed via flow cytometry to quantify CD34⁺, CD34⁺CD38⁺, CD34⁺CD38^-, and CD34⁺CD38^-h-MICL⁺ cell subsets.

A significant increase in circulating CD34⁺CD38^-h-MICL⁺ cells was observed in patients with overt MF (median 2.8%), prefibrotic MF (4.15%), and post-PV/ET MF (3%) compared to PV and ET (median 0%; p < 0.001). A threshold of ≥ 0.9% CD34⁺CD38^-h-MICL⁺ cells effectively identified MF cases with 88% sensitivity and 89% specificity. Moreover, a positive correlation was found between the percentage of CD34⁺CD38^-h-MICL⁺ cells and DIPSS score (ρ = 0.41, p = 0.036), with every 1.72% increase in this cell population corresponding to a 1-point rise in DIPSS score.

Circulating CD34⁺CD38^-h-MICL⁺ cells represent a promising biomarker; their quantification may aid in subclassification, particularly in distinguishing prefibrotic MF from ET, and may serve as a potential target for future therapeutic strategies. Further validation in larger cohorts is warranted.

Schwannomas are exceedingly rare in the tongue. Here, we report clinicopathological features of tongue schwannomas diagnosed at the section of Histopathology, Department of Pathology and Laboratory Medicine, Aga Khan University Hospital (AKUH), Karachi, Pakistan and reviewed the published literature.

Retrospective study of 34 tongue schwannomas diagnosed between 2011 and 2024. Hematoxylin and Eosin (H&E) and immunohistochemical (IHC) slides were reviewed. Demographic and clinical data were obtained.

There was a slight female preponderance. Mean age was 30 years. Commonest sites were lateral borders and base of tongue. All tumors were surgically excised. Average tumor size was 2 cm. Histologically, 30 tumors exhibited classical features of schwannoma, while 4 were cellular. On IHC, strong and diffuse positivity of S100 protein and SOX10 was seen. No recurrences were reported in the cases where follow-up was available. None of the 34 cases had clinical features suggestive of Neurofibromatosis.

Schwannomas although rare, should be included in the differential diagnosis of tongue masses. Early recognition and surgical excision result in excellent outcomes.

Glioma recurrence after surgery remains prevalent, significantly impacting patient survival. Tumor progression is closely linked to metabolic reprogramming, especially abnormalities involving glycolipid metabolism. The triglyceride-glucose (TyG) index accurately indicates insulin resistance (IR) and metabolic disturbances. Although these metabolic indicators are prognostically valuable in various cancers, their role in forecasting glioma recurrence is still insufficiently investigated.

The medical records of 302 primary glioma patients who received surgical treatment at Linyi People's Hospital from 2016 to 2024 were retrospectively reviewed. Participants admitted to one ward (n = 236) were randomly assigned to either a training set (n = 141) or an internal validation set (n = 95). Another distinct ward provided patients (n = 66) for an independent internal validation group. In the training cohort, essential glycolipid metabolic parameters were identified via Bootstrap resampling combined with Least Absolute Shrinkage and Selection Operator (LASSO) regression, yielding a stabilized Bootstrap-LASSO Score (BSL-Score). Clinical variables alongside this score were subjected to univariate Cox regression analysis, and variables with statistical significance (P < 0.05) progressed into multivariate Cox regression to pinpoint independent prognostic indicators. Subsequently, these independent indicators were integrated into a nomogram to forecast 1-, 2-, and 3-year postoperative recurrence-free survival (RFS). Model performance was confirmed through concordance index (C-index) evaluation, time-dependent receiver operating characteristic (ROC) analyses, calibration curves, and decision curve analysis (DCA), with Bootstrap correction utilized for the C-index.

In the training cohort (n = 141), the nomogram achieved a C-index of 0.747 (95% CI: 0.676-0.818) and area under the curve (AUC) values of 0.832, 0.732, and 0.732 for 1‑, 2‑, and 3‑year RFS, respectively. In internal validation (n = 95), the C-index was 0.703 (95% CI: 0.584-0.807); in independent internal validation (n = 66), it was 0.785 (95% CI: 0.694-0.874). Calibration curves showed good agreement, and decision curve analysis confirmed clinical net benefit. The BSL‑Score, derived from routine metabolic parameters (TyG, triglyceride‑to‑high‑density lipoprotein cholesterol ratio (TG/HDL‑C), and TyG‑body mass index (TyG‑BMI)), was an independent predictor of recurrence (multivariate Cox, P < 0.05). Risk stratification by the median nomogram score significantly distinguished high‑risk from low‑risk patients (log‑rank P < 0.001).

The established nomogram effectively integrates preoperative glycolipid metabolic indicators with key clinical factors, accurately stratifying recurrence risk in postoperative glioma patients. It serves as a valuable reference for personalized postoperative monitoring, where risk-adapted surveillance and intervention strategies could optimize patient outcomes.

The internet has become an important source of information for cancer patients. Numerous websites provide nutritional advice that promises benefits for the outcome of cancer therapy. The aim of our study was to evaluate and compare the online information about cancer diets on German- and English-language websites.

A patient's online search was simulated using the search engines Google and Bing. Websites were evaluated by means of content and formal criteria according to a standardized instrument.

The analysis of 31 websites revealed heterogeneous quality regarding content and formality, distributed evenly among the German- and English-language websites. The quality of content and formality does not correlate with the website's order of appearance in a browser-based search.

The high discrepancy in quality of content and formality represents a risk for cancer patients, who are searching for information online. Content of poor quality and formality increases the risk of mal-information and consecutive false decisions on diet. It results in the decline of therapy response, an increased probability of therapeutic toxicity and a poorer prognosis in general. The visibility of high-quality websites needs to be improved.

Increased Src kinase activity is known to correlate with cancer progression and poor prognosis, indicating that Src plays a central role in cell migration and invasion. In this study, we investigated the effects of saracatinib, a Src kinase inhibitor, under anoikis-resistant conditions in colorectal cancer cells.

Wild-type and 5-fluorouracil-resistance acquired SNU-C5 colorectal cancer cells were cultured in both monolayer and spheroid systems under fetal bovine serum (FBS) or growth factor (GF) supplemented conditions. Cell viability assay, flow cytometry, wound healing assay, spheroid formation and morphometric analysis, and Western blotting were performed using both adherent cells and spheroids.

Saracatinib significantly reduced cell viability and migration in both cell lines, predominantly through the induction of apoptosis. Spheroid formation was less efficient under GF-supplemented conditions than under FBS-supplemented conditions. The anti-cancer effects of saracatinib were mediated through inhibition of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated protein kinase (ERK), or epidermal growth factor receptor (EGFR) signaling pathways. Although most cancer stem cell (CSC) markers were suppressed by saracatinib, expression of sex determining region Y-box-2 (Sox2) was paradoxically increased in monolayer cultures. Upon re-treatment with saracatinib, Sox2-upregulated cells formed larger spheroids under GF-supplemented conditions compared with wild-type cells.

Saracatinib exerts anti-cancer effects in colorectal cancer cells by downregulating MAPKs, EGFR, and CSC-associated markers. However, paradoxical upregulation of Sox2 influenced spheroid formation under GF-supplemented conditions, suggesting that Sox2 may contribute to drug resistance or recurrence in colorectal cancers.

The role of 4-hydroxyphenylpyruvate dioxygenase-like protein (HPDL) in endometrial cancer (EC) progression remains poorly understood, particularly its involvement in metabolic-epigenetic crosstalk via lactate-driven histone lactylation. This study aimed to investigate HPDL's mechanistic contribution to EC pathogenesis.

Stable HPDL-overexpressing and knockdown EC cell lines (HEC-1-B and AN3CA) were generated using lentiviral vectors. Functional assays (proliferation, migration, invasion), subcutaneous xenograft models in BALB/c nude mice, and molecular analyses were conducted. Lactate levels, Pan-lysine lactylation (pan-kla), histone H3K18 lactylation (H3K18la), and effects of sodium oxamate (lactate modulator) were assessed. Lactate Dehydrogenase A/Lactate Dehydrogenase B (LDHA/LDHB) knockdown, promoter activity assays, and chromatin immunoprecipitation (ChIP) were performed to evaluate H3K18la occupancy at LDHA/LDHB promoters.

HPDL knockdown reduced intracellular lactate, Pan-Kla, and H3K18la levels, while overexpression elevated these markers. Sodium oxamate amplified lactate and lactylation in HPDL-overexpressing cells but suppressed histone lactylation independently of HPDL. LDHA/LDHB knockdown diminished lactylation, repressed HPDL expression, and inhibited promoter activity. ChIP revealed H3K18la enrichment at LDHA/LDHB promoters in HPDL-overexpressing cells and reduced occupancy in knockdown models. HPDL enhanced EC cell proliferation, migration, and invasion in vitro. In vivo, HPDL-overexpressing xenografts exhibited accelerated tumor growth and larger volumes compared to controls.

HPDL regulates histone lactylation via LDHA/LDHB and promotes the proliferation of EC cells.

Cancer cells are characterized by the ability to exit reversibly from the cell cycle to resist an unfavorable environment. This study elucidates alterations in adhesion molecule expression in melanoma cells acquiring resistance to dacarbazine (DTIC) and entering the G0 state. Plexin A2 (PLXNA2) was identified as a focal adhesion-related molecule implicated in carcinogenesis.

Applying siRNA-mediated knockdown, the effects of altered PLXNA2 expression in melanoma cells were evaluated. PLXNA2 expression was determined by real-time quantitative reverse transcription PCR, immunoblotting, and immunocytochemistry. Cell cycle phase distribution among dacarbazine-treated cells and their apoptosis levels were quantified by flow cytometry, while adhesion to fibronectin was evaluated spectrophotometrically.

Our findings indicated that DTIC treatment modulates melanoma cell interactions with the extracellular matrix, facilitating adhesion to collagen IV, fibronectin, and laminin. Concurrently, integrin expression diminishes upon DTIC exposure. Delete Crucially, focal adhesion signaling molecules, including PLXNA2, Phosphoinositide-3-Kinase Regulatory Subunit 1, and Fibroblast Growth Factor Receptor 2, exhibit increased expression. PLXNA2 knockdown in DTIC-treated melanoma cells did not affect the percentage of cells residing in the G0 phase of the cell cycle. However, it induced apoptosis in DTIC-treated SK-MEL-2 and A375 melanoma cells and G1 cell cycle arrest in A375 melanoma cells.

These findings suggest that PLXNA2 down-regulation in DTIC-treated cancer cells promotes their apoptosis. Therefore, targeting focal adhesion molecules during chemotherapy can increase the sensitivity of tumor cells to anticancer treatment.