Latest Research
All publications from the Cancer3.AI database, newest first.
DLK1 - a novel therapeutic target in cancer.
Henry Pittaway JF
This review article examines DLK1 (Delta-like non-canonical Notch ligand 1), a cell-surface protein that is highly active during embryonic development but largely silenced in healthy adult tissues, as a promising new therapeutic target in cancer. The authors found that DLK1 is consistently re-expressed across a wide range of malignancies, with the highest prevalence in endocrine and neuroendocrine tumours including adrenocortical carcinoma, phaeochromocytoma, paraganglioma, medullary thyroid carcinoma, and neuroblastoma, where its presence correlates with worse clinical outcomes and a treatment-resistant, stem-like tumour state. Because DLK1 is located on the tumour cell surface and largely absent from normal adult tissues, it represents an ideal precision target that could spare healthy cells from therapeutic damage. Multiple DLK1-directed strategies are advancing through preclinical and early clinical stages, including antibody-drug conjugates, CAR-T cell therapies, dendritic cell vaccines, afucosylated monoclonal antibodies, and radioimmunotherapy, with early-phase data showing encouraging safety profiles and early signs of efficacy. The review also highlights that tumour-specific biological factors—such as steroidogenesis, the immune microenvironment, and drug efflux mechanisms—may shape patient responses to DLK1-targeted treatments in endocrine cancers. For patients with rare and difficult-to-treat endocrine malignancies where therapeutic options are currently very limited, DLK1 represents a significant new frontier in precision oncology.
Endocrine-related cancer
Source →Approach to the Patient with Metastatic Pheochromocytoma and Paraganglioma: Advances in Systemic Therapy.
Glover M, et al
This comprehensive review examines the rapidly evolving treatment landscape for metastatic pheochromocytoma and paraganglioma (MPPGL), rare tumors originating from chromaffin cells of the adrenal glands and surrounding tissues, affecting approximately 25% of all pheochromocytoma and paraganglioma patients. The authors outline the full spectrum of systemic therapies, including conventional cytotoxic chemotherapy with cyclophosphamide, vincristine, and dacarbazine, as well as targeted radiopharmaceuticals and multi-target tyrosine kinase inhibitors such as sunitinib and cabozantinib, which have demonstrated meaningful disease control in prospective clinical trials. Most significantly, belzutifan—a first-in-class hypoxia-inducible factor-2α (HIF-2α) inhibitor—recently received US FDA approval as the first oral therapy specifically indicated for MPPGL, offering durable tumor responses, improved blood pressure control, and preserved quality of life. The authors present a practical clinical algorithm that integrates each patient's tumor genotype and clinical phenotype to guide individualized treatment selection, recognizing the biological heterogeneity of these tumors. This review underscores the critical importance of multidisciplinary management for these biologically complex and rare malignancies, providing clinicians with a contemporary framework to optimize care for their patients.
The Journal of clinical endocrinology and metabolism
Source →Characterization of Von Hippel Lindau Gene Variants in an African American Cohort.
Shao YF, et al
This study examined variants in the Von Hippel-Lindau (VHL) gene among Black and African American patients, a population that has been significantly underrepresented in hereditary cancer genetics research. Researchers reviewed germline genetic testing records from 38 Black/African American patients tested at a certified laboratory between November 2014 and March 2022, cataloguing pathogenic variants and classifying patients into established VHL disease subtypes. Hemangioblastoma and pheochromocytoma were the most common tumors in patients' personal cancer histories (each 16%), renal cell carcinoma was the most frequent cancer in family histories (8%), and Type 1 VHL disease was the predominant subtype, accounting for 34% of cases. Substitution variants made up 76% of all identified genetic changes, with p.Arg167Trp being the single most common substitution (8%), while several variants — including p.Pro81Leu, p.Leu129Pro, p.Asp121Val, p.His110Profs*49, and p.Arg82His — appear to be unique to this population. These findings highlight meaningful genetic diversity in VHL disease across racial groups and provide a critical foundation for improving equitable genetic counseling, diagnosis, and clinical management for Black and African American patients with hereditary cancer predisposition syndromes.
HGG advances
Source →Robotic central pancreatectomy in pediatric patients: a systematic review and technical innovation of externalized duct stent reconstruction.
Cattelani A, et al
Researchers conducted a systematic review and technical case series examining robotic central pancreatectomy (CP) — a tissue-sparing surgical procedure — in pediatric patients with benign or low-grade malignant pancreatic tumors. A search of major medical databases identified only ten published case reports of robotic pancreatic surgery in children, with the most common indication being solid pseudopapillary tumor, highlighting just how rare this approach remains in young patients. The authors also described a novel reproducible surgical technique applied in two pediatric patients, combining robotic CP with a Roux-en-Y duct-to-mucosa pancreaticojejunostomy and an externalized pancreatic duct stent — a method borrowed from adult surgery intended to reduce the risk of postoperative pancreatic fistula (POPF), a serious complication involving leakage of pancreatic fluid. Both children experienced minor to moderate complications (one biochemical leak and one grade B POPF) that resolved without reoperation, and at six months both retained normal pancreatic function with no sign of tumor recurrence. The study demonstrates that this approach is technically feasible in carefully selected children, though the extremely limited evidence base means no firm conclusions about its superiority can yet be drawn. The authors call for multicenter studies to validate the technique and establish clearer guidelines for robotic pancreatic surgery in the pediatric population.
Journal of robotic surgery
Source →High tumor mutational burden and PIK3CA mutations correlate with poor Merkel cell carcinoma-specific survival.
Lobo M, et al
Researchers investigated Merkel cell carcinoma (MCC), a rare and aggressive neuroendocrine skin cancer with a poor prognosis, to determine whether specific genetic alterations and tumor mutational burden (TMB) influence patient survival. Using comprehensive genomic profiling data from 164 patients with a mean age of 72.4 years, the team employed Kaplan-Meier survival analysis and multivariable Cox regression to identify genetic predictors of MCC-specific survival. The study found that patients with high TMB had significantly worse survival outcomes compared to those with low TMB, and that mutations in the PIK3CA gene — encoding a key enzyme in the PI3K cell-growth signaling pathway — were independently associated with more than double the risk of MCC-related death (hazard ratio 2.07). PIK3CA remained a robust predictor of poor survival across multiple sensitivity analyses, suggesting it is a reliable prognostic biomarker. These findings may help clinicians stratify MCC patients by risk level, enabling more personalized monitoring and treatment planning. The results also provide a scientific rationale for evaluating PI3K pathway inhibitors as a potential therapeutic strategy in future MCC clinical trials.
JCI insight
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