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Ultrasound-Guided Orthotopic Implantation of Murine Pancreatic Ductal Adenocarcinoma
Published on: November 19, 2019
Genomic profiling in pancreatic ductal adenocarcinoma and a pathway towards therapy individualization: A scoping
Ritu R Singh1, Johanna Goldberg2, Anna M Varghese3
1Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai St. Luke's and Mount Sinai West, New York, NY 10019, USA.
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.
Insights
Genomic targeted therapies show promise for pancreatic cancer (PDAC), with established efficacy for DNA repair gene mutations and mismatch repair deficiency. However, targeting common KRAS mutations requires further research.
Area of Science:
- Oncology
- Genomics
- Translational Research
Background:
- Pancreatic ductal adenocarcinoma (PDAC) remains a challenging cancer with limited treatment advancements.
- Individualized therapy based on genomic alterations is gaining traction in PDAC management.
Purpose of the Study:
- To systematically review therapies targeting somatic and germline alterations in PDAC.
- To evaluate downstream pathways affected by these genomic alterations.
Main Methods:
- A systematic literature search adhering to PRISMA guidelines was performed.
- Studies published after January 1, 2008, were included.
Main Results:
- 71 studies were analyzed, focusing on KRAS-pathway (36 studies, MEK inhibitors), DNA damage repair genes (22 studies, platinum/PARP inhibitors), and mismatch repair deficiency/microsatellite instability (immunotherapy).
- Promising results were observed for platinum-based chemotherapy and PARP inhibitors in patients with DNA damage repair gene mutations.
- Immunotherapy demonstrated activity in patients with mismatch repair deficiency/microsatellite instability.
Conclusions:
- Genomic targeted therapies offer a promising avenue for PDAC treatment.
- Targeting BRCA mutations with platinum/PARP inhibitors and microsatellite instability with immunotherapy is validated.
- Further research is needed to target common driver oncogenes, especially in the KRAS-wild type PDAC subgroup.
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