Genomic profiling in pancreatic ductal adenocarcinoma and a pathway towards therapy individualization: A scoping review Review
| Authors: | Singh, R. R.; Goldberg, J.; Varghese, A. M.; Yu, K. H.; Park, W.; O'Reilly, E. M. |
| Review Title: | Genomic profiling in pancreatic ductal adenocarcinoma and a pathway towards therapy individualization: A scoping review |
| Abstract: | Context: Pancreatic cancer (PDAC) is one of the most challenging cancers to treat with modest recent improvements in survival from new systemic therapies. There is growing interest in individualized therapy underpinned by somatic and germline genomic alterations. Objective: A systematic review of data on therapies targeting somatic and germline alterations, and their downstream pathways in PDAC. Method: A systematic literature search was conducted using PRISMA guidelines to include relevant results published after January 1, 2008. Results: A total of 71 relevant studies were included. We identified 36 studies targeting the KRAS-pathway, the most common being with MEK-inhibitor therapy. Twenty-two studies were identified that evaluated platinum-based chemotherapy and PARP inhibitors in patients with deleterious mutations in DNA damage repair genes and have shown encouraging results. Immunotherapy has demonstrated activity in patients with mismatch repair deficiency/microsatellite instability. Conclusion: Evidence from translational and clinical research presents an exciting platform for genomic targeted therapy in PDAC. Validity for targeting BRCA with platinum and PARP inhibitors and microsatellite instability with immune therapy has been established, nonetheless, evidence for targeting the common driver oncogenes is lacking and much work is needed. Of importance is identifying the subgroup of KRAS -wild type PDAC (approximately 5%) where there is enrichment for targetable opportunities. © 2019 Elsevier Ltd |
| Keywords: | somatic mutation; drug tolerability; review; sorafenib; erlotinib; placebo; cancer combination chemotherapy; drug efficacy; drug safety; monotherapy; unspecified side effect; drug targeting; capecitabine; gemcitabine; paclitaxel; cancer radiotherapy; antineoplastic agent; dna repair; unindexed drug; cancer immunotherapy; mitogen activated protein kinase inhibitor; small interfering rna; rna interference; drug dose escalation; rash; systematic review; mismatch repair; microsatellite instability; drug response; tipifarnib; single drug dose; pancreas adenocarcinoma; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase inhibitor; drug cytotoxicity; platinum complex; oncogene k ras; peptide vaccine; chemoradiotherapy; epidermal growth factor receptor kinase inhibitor; pertuzumab; personalized medicine; salirasib; phosphatidylinositol 3 kinase inhibitor; molecularly targeted therapy; germline mutation; selumetinib; mitogen activated protein kinase kinase inhibitor; trametinib; afatinib; 8 [4 (1 aminocyclobutyl)phenyl] 9 phenyl 1,2,4 triazolo[3,4 f][1,6]naphthyridin 3(2h) one; pimasertib; dna damage repair; buparlisib; human; pancreatic ductal adenocarcinoma (pdac); rigosertib; cobimetinib; genomic alteration (ga); mismatch repair (mmr); pelareorep; ravoxertinib; refametinib |
| Journal Title: | Cancer Treatment Reviews |
| Volume: | 75 |
| ISSN: | 0305-7372 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2019-05-01 |
| Start Page: | 27 |
| End Page: | 38 |
| Language: | English |
| DOI: | 10.1016/j.ctrv.2019.03.003 |
| PUBMED: | 30927677 |
| PROVIDER: | scopus |
| PMCID: | PMC6504563 |
| DOI/URL: | |
| Notes: | Review -- Export Date: 1 May 2019 -- Source: Scopus |
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