Latest Research
All publications from the Cancer3.AI database, newest first.
Mitochondrial ACSS1 Links Acetate Metabolism to Pyrimidine Biosynthesis in Nutrient-Stressed B-Cell Lymphomas.
Basappa J, et al
Researchers investigated how cancer cells in B-cell lymphomas, including mantle cell lymphoma, diffuse large B-cell lymphoma, and chronic lymphocytic leukemia, survive in nutrient-poor tumor environments by exploiting alternative carbon sources such as acetate. The study identifies ACSS1, a mitochondrial enzyme, as a critical metabolic driver that converts acetate into acetyl-CoA, fueling energy production and biosynthetic processes when nutrients are scarce. Crucially, the researchers discovered that ACSS1 links acetate metabolism directly to the production of pyrimidines, the building blocks of DNA and RNA, through the TCA cycle intermediates aspartate and dihydroorotate — a previously unknown metabolic connection. Silencing ACSS1 in lymphoma cells impaired mitochondrial respiration and pyrimidine synthesis, and these defects could be rescued by supplying acetate or uridine, confirming the functional importance of this pathway. In mouse models of mantle cell lymphoma, suppressing ACSS1 dramatically reduced tumor growth, validating its relevance beyond cell culture experiments. These findings reveal ACSS1 as a novel therapeutic target whose inhibition could cut off a vital metabolic lifeline in aggressive B-cell lymphomas, opening new avenues for drug development.
Cancer letters
Source →A novel activating somatic mutation in EPAS1, coding for HIF-2α, in a patient with a paraganglioma and sickle cell disease.
Shekhda KM, et al
Researchers report a rare case of a young woman with sickle cell disease who developed a paraganglioma, a tumor arising from nerve tissue near the aorta, linked to a newly identified activating mutation in the EPAS1 gene encoding the protein HIF-2α. The study examined how chronic low-oxygen conditions caused by sickle cell anemia and associated kidney disease may promote abnormal activation of hypoxia-signaling pathways, increasing susceptibility to these rare tumors. Genetic analysis revealed that the patient carried a likely pathogenic somatic mutation in EPAS1, but did not carry mutations in other commonly tested paraganglioma predisposition genes, highlighting EPAS1 as a distinct and underrecognized culprit. The findings suggest that patients with sickle cell disease face an elevated risk of developing pheochromocytomas and paragangliomas due to chronic hypoxia-driven overactivation of HIF-2α signaling. Clinicians are urged to maintain a higher index of suspicion for these tumors when evaluating patients with sickle cell disease, and to consider EPAS1 mutation testing even when standard genetic panels return negative results.
Archives of endocrinology and metabolism
Source →A case of multiple type I endocrine neoplasia with gastrin-producing and glucagon-producing tumors successfully resected 18 years after insulinoma surgery.
Miyata T, et al
Researchers report a rare and complex case of Multiple Endocrine Neoplasia type 1 (MEN1), a hereditary condition causing tumors in multiple hormone-producing glands, in a 27-year-old woman who had previously undergone surgery for an insulin-producing tumor 18 years earlier. Advanced imaging and a specialized diagnostic test called selective arterial calcium injection identified both a gastrin-producing tumor and a glucagon-producing tumor in different parts of the pancreas. Surgical removal revealed 15 tiny gastrin-producing tumors in the duodenum and pancreatic head, along with six lymph node metastases, while the pancreatic tail tumor proved to be glucagon-producing. The successful curative resection was made possible by precise localization techniques and careful long-term follow-up spanning nearly two decades. This case highlights the critical importance of ongoing surveillance in MEN1 patients, as different hormone-secreting tumors can develop simultaneously or at widely separated points in time, requiring clinicians to remain vigilant throughout a patient's lifetime.
Clinical journal of gastroenterology
Source →A metabolomics and lipidomics atlas of pulmonary large cell neuroendocrine carcinoma.
Tietzova I, et al
Researchers conducted the first comprehensive metabolomics and lipidomics atlas of pulmonary large cell neuroendocrine carcinoma (LCNEC), a rare and aggressive lung cancer subtype with few treatment options. Using tumor and adjacent healthy tissue samples from 34 patients, the team profiled over 1,000 metabolites and lipids through advanced mass spectrometry techniques. Key findings included abnormal accumulation of 2-hydroxyglutaric acid pointing to disrupted energy metabolism, elevated N-lactoyl-amino acids linked to high lactate activity, and widespread lipid remodeling affecting cell membranes, fat storage, and mitochondrial function. The study also demonstrated that the nicotine byproduct cotinine could serve as an objective smoking biomarker, revealing that some patients had misreported their smoking habits. These discoveries define a unique metabolic fingerprint for LCNEC that bridges features of both small cell and non-small cell lung cancers, offering a foundation for developing new biomarkers and targeted, metabolism-based therapies for this understudied disease.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
Source →Pulmonary Carcinoid Tumors and DIPNECH: Surgical Perspectives on a Rare and Evolving Spectrum of Lung Neuroendocrine Disease.
Gawdi R, et al
A new review published in The Journal of Thoracic and Cardiovascular Surgery examines the full clinical spectrum of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) and related pulmonary neuroendocrine tumors, collectively termed DIPNECH-spectrum lesions. These rare lung conditions involve abnormal proliferation of neuroendocrine cells and can range from premalignant changes to slow-growing tumors, often discovered incidentally on CT screening scans. The authors synthesize current evidence on how these lesions should be diagnosed, staged, and surgically managed, addressing key questions such as when to operate, how much lung tissue to remove, and how to handle cases where multiple tumors are present simultaneously. The review highlights that thoracic surgeons increasingly encounter these lesions yet face significant uncertainty because DIPNECH-spectrum disease occupies a gray zone between benign precursor conditions and true malignancy. As lung cancer screening programs expand and detect more of these asymptomatic neuroendocrine lesions, clinicians need updated, evidence-based frameworks to guide treatment decisions and long-term patient follow-up. This work calls for a paradigm shift in how thoracic surgery approaches these unusual tumors, underscoring the need for individualized management strategies informed by emerging translational research into how these lesions progress to cancer.
The Journal of thoracic and cardiovascular surgery
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