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Browsing by Author "Von Holzen, Urs"
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Item A case of squamous cell lung cancer presented as a cystic lesion and recurrent pneumothoraces(Elsevier, 2021-03-09) Aldaghlawi, Fadi; Von Holzen, Urs; Li, Liang; Hadid, Walid; Medicine, School of MedicineWe report a rare case of a 70-year-old male with recurrent pneumothoraces within one year treated with intermittent insertion of chest tube on each occasion. Diagnostic testing was notable for a cystic lesion in the left lung that was initially interpreted as bulla on chest x-ray and chest computed tomographic scan. Due to thickening and nodularity changes of the thin wall of the cystic lesion, the patient underwent left upper lobectomy. Pathology showed poorly differentiated squamous cell carcinoma of the cystic lesion wall. This case emphasizes the importance of monitoring pulmonary cystic lesions especially in patients with a history of smoking and emphysema.Item Targeting KRAS for the potential treatment of pancreatic ductal adenocarcinoma: Recent advancements provide hope (Review)(Spandidos Publications, 2023) Zhang, Joshua; Darman, Lily; Hassan, Md Sazzad; Von Holzen, Urs; Awasthi, Niranjan; Surgery, School of MedicineKirsten rat sarcoma viral oncogene homolog (KRAS) is one of the most frequently mutated oncogenes in solid tumors. More than 90% of pancreatic ductal adenocarcinoma (PDAC) are driven by mutations in the KRAS gene, suggesting the importance of targeting this oncogene in PDAC. Initial efforts to target KRAS have been unsuccessful due to its small size, high affinity for guanosine triphosphate/guanosine diphosphate, and lack of distinct drug‑binding pockets. Therefore, much of the focus has been directed at inhibiting the activation of major signaling pathways downstream of KRAS, most notably the PI3K/AKT and RAF/MAPK pathways, using tyrosine kinase inhibitors and monoclonal antibodies. While preclinical studies showed promising results, clinical data using the inhibitors alone and in combination with other standard therapies have shown limited practicality, largely due to the lack of efficacy and dose‑limiting toxicities. Recent therapeutic approaches for KRAS‑driven tumors focus on mutation‑specific drugs such as selective KRASG12C inhibitors and son of sevenless 1 pan‑KRAS inhibitors. While KRASG12C inhibitors showed great promise against patients with non‑small cell lung cancer (NSCLC) harboring KRASG12C mutations, they were not efficacious in PDAC largely because the major KRAS mutant isoforms in PDAC are G12D, G12V, and G12R. As a result, KRASG12D and pan‑KRAS inhibitors are currently under investigation as potential therapeutic options for PDAC. The present review summarized the importance of KRAS oncogenic signaling, challenges in its targeting, and preclinical and clinical targeted agents including recent direct KRAS inhibitors for blocking KRAS signaling in PDAC.