Reference Detail

Ref Type

PMID

(33250737)

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	Vol	Issue	Date	Pages	Journal Short Title
Case reports in oncology	13	3	2020 Sep-Dec	1239-1243	Case Rep Oncol

URL

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.

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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, PMID: 37379264), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Sep 2023).

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