Next-Generation Sequencing in the Era of Cancer-Targeted Therapies: Towards the Personalised Medicine

2015 ◽  
pp. 39-55
Author(s):  
Ashwag Albukhari ◽  
Fawzi F. Bokhari ◽  
Hani Choudhry
Keyword(s):  
Next Generation Sequencing ◽  
Targeted Therapies ◽  
Personalised Medicine ◽  
Next Generation ◽  
Generation Sequencing

Next-generation sequencing for guiding matched targeted therapies in people with relapsed or metastatic cancer

2021 ◽  
Vol 2021 (10) ◽  
Author(s):  
Farasat Kazmi ◽  
Nipun Shrestha ◽  
Stephen Booth ◽  
David Dodwell ◽  
Francesca Aroldi ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Targeted Therapies ◽  
Metastatic Cancer ◽  
Next Generation ◽  
Generation Sequencing

Therapeutic impact and timing of gastrointestinal malignancy genomic profiling: A single-institution experience.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 584-584
Author(s):  
Kristin Lynn Koenig ◽  
Jarred Burkart ◽  
Sameh Mikhail ◽  
Christina Sing-Ying Wu ◽  
Anne M. Noonan ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Next Generation Sequencing ◽  
Targeted Therapies ◽  
Clinical Care ◽  
Comprehensive Cancer Center ◽  
Genomic Profiling ◽  
Next Generation ◽  
Wild Type ◽  
Genomic Alterations ◽  
Generation Sequencing

584 Background: Tumor genomic profiling has become critical in the identification of targeted therapeutic options for patients (pts) with advanced malignancies. Mutational frequencies and their therapeutic importance vary among tumor types. This analysis was undertaken to characterize the landscape of genomic alterations in gastrointestinal (GI) malignancies found in a large academic institutional practice, and to determine the frequency of alteration-specific targeted therapy selection based on genomic profiling. Methods: Adult pts with GI malignancies presenting to the Ohio State University Comprehensive Cancer Center oncology clinics were offered next generation sequencing through FoundationOne testing as part of routine clinical care. Institutional review board approval was obtained to retrospectively analyze results from FoundationOne testing performed between 2012 and 2015. Results: 265 pts with GI malignancies underwent successful genomic profiling. 1205 genomic alterations were found, with an average of 4.5 per tumor (range 0-20); 365 (30%) of these were potentially actionable and most often found in colorectal or gastroesophageal tumors. 14 pts (5.3%) had actionable alterations in MET, CDKN2A/B, FGFR2, KRAS, BRAF, or NF2 that led to enrollment in genotype-directed clinical trials or off label use of targeted therapies beyond standard of care. Pt performance status at the time of genomic alteration identification was a significant factor in precluding genotype-directed therapy. One variant of unknown significance involving FGFR2 identified at initial testing subsequently became actionable and led to pt enrollment on a clinical trial. One pt with rectal cancer was found to have a KRAS wild-type and BRAF mutant primary but KRAS mutant and BRAF wild-type liver metastasis. Conclusions: Genomic profiling of GI malignancies through next generation sequencing is feasible and can lead to genotype-directed therapy selection; however, it should be considered early in the pt’s course to optimize use of targeted therapies through clinical trials. Consideration should be given to serial tumor testing to identify emerging genomic alterations for optimal therapy selection.

scholarly journals Next-Generation Sequencing: Targeting Targeted Therapies

2015 ◽  
Vol 21 (16) ◽  
pp. 3584-3585 ◽  
Author(s):  
Justine N. McCutcheon ◽  
Giuseppe Giaccone
Keyword(s):  
Next Generation Sequencing ◽  
Targeted Therapies ◽  
Next Generation ◽  
Generation Sequencing

scholarly journals Clinical Targeted Next-Generation Sequencing to Identify Potentially Actionable Alterations in the Majority of Asian Cancer Patients

2018 ◽  
Vol 4 (Supplement 2) ◽  
pp. 88s-88s
Author(s):  
S.L. Poon ◽  
Y.-J. Lu ◽  
R.-S. Jhou ◽  
Y.-T. Yang ◽  
P.-N. Yu ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Targeted Therapies ◽  
Hedgehog Signaling ◽  
Next Generation ◽  
Therapeutic Implications ◽  
Targeted Next Generation Sequencing ◽  
Formalin Fixed Paraffin Embedded ◽  
Ffpe Tissues ◽  
Tumor Types ◽  
Generation Sequencing

Background: Clinically innovative genomic diagnostics may expedite the selection of effective targeted therapies if the patient can be stratified correctly based on their unique cancer driven events/pathways during tumorigenesis. Aim: Here, we performed a pan-cancer analysis on the clinical utility of a targeted gene panel, ACTOnco+, in characterizing the prevalence of actionable mutations. Methods: A total of 229 formalin-fixed, paraffin-embedded (FFPE) tissues from 40 tumor types were subjected to next-generation sequencing (NGS) using the Ion Torrent Proton System. All coding exons in 440 cancer-related genes were assessed at average depth of > 800X. Therapeutic implications were based on information obtained from base substitutions, indels, and copy number alterations (CNAs). Results: 58.5% (n=134) patients harbored at least one actionable mutation while CNAs, including homozygous and heterozygous deletions, were detected in 83.9% (n=191) of patients. Across all tumor types, the most frequently altered pathway that can confer either sensitivity or resistance to targeted therapies was PI3K/AKT/mTOR signaling, contributed by PIK3CA and AKT1 activating mutations as well as NF1, NF2, PTEN, TSC1, STK11 and TSC2 inactivating mutations or deletions. In parallel, dysregulation of cell cycle was mostly owing to CCND1, CDK4 and CDK6 amplification and/or loss of CDKN2A. Notably, on top of BRCA1/ 2 mutations, deletion of BRCAness-related genes ( MRE11, RAD50, PALB2, FANCD2, ATM, ATR, CHEK1 and CHEK2) that may result in homologous recombination deficiency (HRD) was observed in 71.4% breast, 70.6% ovarian, 61.0% lung, 58.3% pancreatic, and 52.2% colorectal cancers. Other targetable alterations on receptor tyrosine kinase (RTK), angiogenic and hedgehog signaling pathways were also observed. Conclusion: A comprehensive pathway-based genomic profiling characterized significant actionable alterations across different solid tumors that may play a role in tissue-agnostic tailored treatment.

Targeted gene sequencing panel for identifying actionable genomic alterations in Taiwanese lung cancer patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20522-e20522
Author(s):  
Yen-Jung Lu ◽  
Kien Thiam Tan ◽  
Chun-Jung Chen ◽  
Ren-Shiang Jhou ◽  
Yi-Ting Yang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Next Generation Sequencing ◽  
Cancer Patients ◽  
Targeted Therapies ◽  
Copy Number ◽  
Egfr Mutations ◽  
Next Generation ◽  
Genomic Alterations ◽  
Lung Cancer Patients ◽  
Generation Sequencing

e20522 Background: Lung cancer boasts an arsenal of targeted therapies directed at various molecular aberrations such as EGFR mutations and fusion genes. Simultaneous assessment for genetic alterations provides biomarkers to assist clinicians in their treatment selections. Methods: A total of 43 FFPE (formalin-fixed, paraffin-embedded) samples obtained from lung cancer patients in Taiwan were subjected to next-generation sequencing (NGS), using a compact panel encompassing 17 potentially actionable, lung cancer-associated genes. NGS was performed on the Ion Torrent PGM or Proton System with a targeted average depth of > 800x. Genomic alterations detected were categorized as single nucleotide variants (SNV) or chromosomal copy number alterations (CNA). Results: A total of 74 putatively actionable genomic alterations were detected across 38 patients (88.4%), which may predict sensitivity or resistance to established and/or therapies that are still in clinical development. 19 patients (44.2%) had tumors harboring activating EGFR mutations in the tyrosine kinase (TK) domain – L858R substitution or exon 19 deletion, which may suggest clinical benefit to first- and second-generation EGFR TK inhibitors (TKIs). Three patients (7.0%) whose tumor had acquired the EGFR T790M mutation were advised to switch to third-generation EGFR TKI. Possible resistance mechanisms to EGFR TKIs via increased copy number of EGFR (14.0%, n = 6) and MET (11.6%, n = 5) were observed. Deletion or loss of CDKN2A gene were detected in 14 patients (32.6%), which may confer sensitivity to CDK4/6 inhibitors. Inhibition of downstream effectors in the RAS/RAF/MEK/ERK and PI3K/AKT/mTOR pathways were suggested for patients whose tumor harbored PIK3CA and/or KRAS oncogenic mutations. Conclusions: Next-generation sequencing using a compact panel of genes may be sufficient to identify biomarkers for targeted therapies selection for most lung cancer patients in Taiwan.

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