title: Identifying pancreatic cancer patients for targeted treatment: the challenges and limitations of the current selection process and vision for the future.
abstract: Recent preclinical data have demonstrated that pancreatic adenocarcinoma (PDA) cells with defects in the Fanconi anemia/BRCA2 pathway are hypersensitive to interstrand crosslinking agents. The challenge is to efficiently identify patients who will benefit from these therapies. Patients were chosen for this study by evaluating personal history, ethnic background and family history of pancreatic malignancy. Molecular assays were performed on tissue samples. Patient A developed PDA in the context of a known BRCA2 frameshift mutation (2157delG), suspected because of her personal and multigenerational family history of breast cancer. She was treated with surgical resection, and targeted chemotherapy. Patient A continues to be disease free 32 months after her diagnosis and treatment. Patient B developed PDA in the context of a strong family history of PDA and Ashkenazi Jewish heritage. Genetic analysis on critical DNA repair genes revealed no alterations. This patient did not receive a tailored treatment regimen. This study highlights the challenge of treating PDA patients and selecting those eligible for targeted therapy. The current targeted treatment options for PDA are reviewed. A new multidisciplinary approach for stratifying PDA patients for promising targeted adjuvant therapy and familial risk counseling is proposed.
authors.affiliation: Thomas Jefferson University, Jefferson Pancreas, Biliary and Related Cancer Center, Jefferson Pancreatic Tumor Registry, Department of Surgery, Suite 611A Curtis Building, Philadelphia, PA 19107, USA.
authors.forename: Shayna L
authors.initials: SL
authors.lastname: Showalter
authors.forename: Sarah
authors.initials: S
authors.lastname: Charles
authors.forename: Justin
authors.initials: J
authors.lastname: Belin
authors.forename: Joseph
authors.initials: J
authors.lastname: Cozzitorto
authors.forename: Peter
authors.initials: P
authors.lastname: Einstein
authors.forename: Nathan G
authors.initials: NG
authors.lastname: Richards
authors.forename: Patricia K
authors.initials: PK
authors.lastname: Sauter
authors.forename: Eugene P
authors.initials: EP
authors.lastname: Kennedy
authors.forename: Agnes
authors.initials: A
authors.lastname: Witkiewicz
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Brody
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Yeo
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D016368:Frameshift Mutation; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D018579:Patient Selection
chemical_list: D000970:Antineoplastic Agents