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|Authors||Sasankan S, Rebuck L, Darrah G, Harari Turquie M, Rabinowitz I|
|Title||Metastatic Pancreatic Cancer with BRAF and P53 Mutations: Case Report of Therapeutic Response to Doublet Targeted Therapy.|
|Journal||Case reports in oncology|
|Abstract Text||We report on the clinical history of a 49-year-old female with metastatic pancreatic cancer. She was initially treated with standard chemotherapy as per current guidelines. She was found to have both a BRAF and P53 mutation, and received dabrafenib and trametinib with deep responses, both radiographically and biochemically (CA19-9). Her response has been more clinically relevant than responses in previous case reports of patients with BRAF-positive pancreatic cancer treated with targeted therapy. To the best of our knowledge, this is the first case report showing a dramatic therapeutic response to combination therapy with dabrafenib and trametinib in metastatic pancreatic cancer.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|TP53||C176R||missense||unknown||TP53 C176R lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). C176R has been identified in the scientific literature (PMID: 33250737), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Feb 2022).|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|BRAF V600E TP53 C176R||pancreatic adenocarcinoma||predicted - sensitive||Dabrafenib + Trametinib||Case Reports/Case Series||Actionable||In a clinical case study, a patient with metastatic pancreatic adenocarcinoma harboring BRAF V600E and TP53 C176R was treated with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) and achieved radiographic and biochemical responses with stabilization or reduction of lesions in the pancreas, lung, and liver, and remained on treatment despite progression of a single liver lesion after 8 months (PMID: 33250737).||33250737|