Case Report: Effectiveness of Targeted Treatment in a Patient With Pancreatic Cancer Harboring PALB2 Germline Mutation and KRAS Somatic Mutation

Pancreatic cancer is one of the most leading causes of cancer death worldwide. The rapid development of next-generation sequencing (NGS) and precision medicine promote us to seek potential targets for the treatment of pancreatic cancer. Here, we report a female pancreatic cancer patient who underwent radical surgical excision after neoadjuvant chemotherapy. After the surgery, the patient underwent gemcitabine + S-1 therapy, capecitabine + albumin paclitaxel therapy and irinotecan therapy successively, however, MRI review revealed tumor progression. The surgical tissue sample was subjected to next-generation sequencing (NGS), and PALB2 germline mutation and KRAS somatic mutation were identified. The patient then received olaparib (a PARP inhibitor) + irinotecan and the disease stabilized for one year. Due to the increased CA19-9, treatment of the patient with a combination of trametinib (a MEK inhibitor) and hydroxychloroquine resulted in stable disease (SD) with a significant decrease of CA19-9. This case demonstrated that the NGS may be a reliable method for finding potential therapeutic targets for pancreatic cancer.

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The applications of next-generation sequencing (NGS) in drug development for cancer therapy

Current Analytical Chemistry ◽

10.2174/1573411016999200626193227 ◽

2020 ◽

Vol 16 ◽

Author(s):

Pelin Telkoparan-Akillilar ◽

Dilek Cevik

Keyword(s):

Next Generation Sequencing ◽

Drug Discovery ◽

Cancer Therapy ◽

Target Identification ◽

Rapid Development ◽

Next Generation ◽

Biomedical Sciences ◽

Dna And Rna ◽

Next Generation Sequencing Ngs ◽

Generation Sequencing

Background: Numerous sequencing techniques have been progressed since the 1960s with the rapid development of molecular biology studies focusing on DNA and RNA. Methods: a great number of articles, book chapters, websites are reviewed, and the studies covering NGS history, technology and applications to cancer therapy are included in the present article. Results: High throughput next-generation sequencing (NGS) technologies offer many advantages over classical Sanger sequencing with decreasing cost per base and increasing sequencing efficiency. NGS technologies are combined with bioinformatics software to sequence genomes to be used in diagnostics, transcriptomics, epidemiologic and clinical trials in biomedical sciences. The NGS technology has also been successfully used in drug discovery for the treatment of different cancer types. Conclusion: This review focuses on current and potential applications of NGS in various stages of drug discovery process, from target identification through to personalized medicine.

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Next-generation sequencing-based BRCA testing on cytological specimens from ovarian cancer ascites reveals high concordance with tumour tissue analysis

Journal of Clinical Pathology ◽

10.1136/jclinpath-2019-206127 ◽

2019 ◽

Vol 73 (3) ◽

pp. 168-171 ◽

Cited By ~ 1

Author(s):

Caterina Fumagalli ◽

Alessandra Rappa ◽

Chiara Casadio ◽

Ilaria Betella ◽

Nicoletta Colombo ◽

...

Keyword(s):

Ovarian Cancer ◽

Next Generation Sequencing ◽

Clinical Decision Making ◽

Parp Inhibitor ◽

Clinical Decision ◽

Tumour Tissue ◽

Next Generation ◽

High Concordance ◽

Next Generation Sequencing Ngs ◽

Generation Sequencing

BackgroundWith the approval of the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib for newly diagnosed, breast cancer gene (BRCA)1/2 mutated, ovarian cancer women, the assessment of BRCA1/2 tumour status will be shortly required at the time of diagnosis.AimTo investigate the feasibility of next-generation sequencing (NGS)-based BRCA tumour test on cytological specimens from ovarian cancer ascites.MethodsWe evaluated the BRCA1/2 status on neoplastic ascites and corresponding tumour tissue of 11 patients with ovarian cancer, using the NGS ‘Oncomine BRCA Research Assay’.ResultsThe NGS-based BRCA test on cytological samples had a success rate of 100%, with 11 of 11 concordant BRCA1/2 results between ascites and tumour tissues analyses, including two wild type samples and nine cases harbouring somatic or germline variants.ConclusionBRCA test may be performed on ovarian cancer ascites, reproducing BRCA1/2 tumour status and representing a useful tool for clinical decision-making.

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Next-generation sequencing and histological response assessment in peritoneal metastasis from pancreatic cancer treated with PIPAC

Journal of Clinical Pathology ◽

10.1136/jclinpath-2020-206607 ◽

2020 ◽

Vol 74 (1) ◽

pp. 19-24 ◽

Cited By ~ 1

Author(s):

Malene Nielsen ◽

Martin Graversen ◽

Signe Bremholm Ellebæk ◽

Thomas Kielsgaard Kristensen ◽

Claus Fristrup ◽

...

Keyword(s):

Pancreatic Cancer ◽

Next Generation Sequencing ◽

Peritoneal Metastasis ◽

Response Assessment ◽

Histological Response ◽

Next Generation ◽

Pancreatic Cancers ◽

Before And After ◽

Next Generation Sequencing Ngs ◽

Generation Sequencing

BackgroundPeritoneal metastasis from pancreatic cancer (PM-PC) may be treated with repeated pressurised intraperitoneal aerosol chemotherapy (PIPAC). Utility of next-generation sequencing (NGS) to detect cancer-related mutations in peritoneal quadrant biopsies (QBs) and peritoneal fluid (PF) after systemic and PIPAC treatment has not been evaluated. Around 90% of pancreatic cancers (PCs) harbour a KRAS mutation, making PC ideal for the evaluation of this aspect.AimsEvaluation of PM-PC in terms of (1) histological response to PIPAC using Peritoneal Regression Grading Score (PRGS), (2) clinical characteristics and (3) frequency of mutations in QBs and PF before and after PIPAC.MethodsPeritoneal QBs and PF were obtained prior to each PIPAC. NGS for 22 cancer-related genes was performed on primary tumours, QBs and PFs. Response was assessed by the four-tiered PRGS.ResultsSixteen patients treated with a median of three PIPAC procedures were included. The mean PRGS was reduced from 1.91 to 1.58 (p=0.02). Fifty-seven specimens (13 primary tumours, 2 metastatic lymph nodes, 16 PFs and 26 QB sets) were analysed with NGS. KRAS mutation was found in 14/16 patients (87.50%) and in QBs, primary tumours and PF in 8/12 (66.67%), 8/13 (61.53%) and 6/9 (66.67%). The median overall survival was 9.9 months (SE 1.5, 95% CI 4.9 to 13.9).ConclusionPIPAC induces histological response in the majority of patients with PM-PC. KRAS mutation can be found in PM-PC after PIPAC at a frequency similar to the primaries. NGS may be used to detect predictive mutations in PM-PC of various origins, also when only post-PIPAC QBs or PFs are available.

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