The Personalization of Therapy: Molecular Profiling Technologies and Their Application

Zerón-Medina, Jorge; Olza, María Ochoa de; Braña, Irene; Rodón, Jordi

doi:10.1053/j.seminoncol.2015.09.026

Cited by 6 publications

(4 citation statements)

References 81 publications

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“…It follows that with the current next generation sequencing capabilities, we are now able to exquisitely tease out the complex genetic information underlying cancer development and concurrently identify relevant gene signatures that are unique to each tumor and link these to drug response with the clear view of identifying new therapies as treatment options192021. Exome sequencing is a cost-effective approach to identify mutational profile, and has been used extensively for discovering driver mutations as well as to uncover new potential treatment strategies for various cancer types.…”

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confidence: 99%

Exome Sequencing Identifies Potentially Druggable Mutations in Nasopharyngeal Carcinoma

Chow

Tan

Chai

et al. 2017

Sci Rep

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In this study, we first performed whole exome sequencing of DNA from 10 untreated and clinically annotated fresh frozen nasopharyngeal carcinoma (NPC) biopsies and matched bloods to identify somatically mutated genes that may be amenable to targeted therapeutic strategies. We identified a total of 323 mutations which were either non-synonymous (n = 238) or synonymous (n = 85). Furthermore, our analysis revealed genes in key cancer pathways (DNA repair, cell cycle regulation, apoptosis, immune response, lipid signaling) were mutated, of which those in the lipid-signaling pathway were the most enriched. We next extended our analysis on a prioritized sub-set of 37 mutated genes plus top 5 mutated cancer genes listed in COSMIC using a custom designed HaloPlex target enrichment panel with an additional 88 NPC samples. Our analysis identified 160 additional non-synonymous mutations in 37/42 genes in 66/88 samples. Of these, 99/160 mutations within potentially druggable pathways were further selected for validation. Sanger sequencing revealed that 77/99 variants were true positives, giving an accuracy of 78%. Taken together, our study indicated that ~72% (n = 71/98) of NPC samples harbored mutations in one of the four cancer pathways (EGFR-PI3K-Akt-mTOR, NOTCH, NF-κB, DNA repair) which may be potentially useful as predictive biomarkers of response to matched targeted therapies.

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confidence: 99%

Exome Sequencing Identifies Potentially Druggable Mutations in Nasopharyngeal Carcinoma

Chow

Tan

Chai

et al. 2017

Sci Rep

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“…In this perspective, the pharmaceutical industry should incorporate pharmacogenomics into development phases of a drug, especially during clinical trials Phase II. Identifying specific genetic profiles for patients may create the basis for the approval and marketing of a specific medicine for a population [42][43][44][45].…”

Section: Resultsmentioning

confidence: 99%

Personalized Medicine and Adverse Drug Reactions: The Experience of An Italian Teaching Hospital

Russa

Fineschi

Sanzo

et al. 2017

CPB

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“…This includes determination of the somatic nature of a mutation in the absence of germ line sequence, the difficulty of robustly calling low-abundance variants, or sequencing artifacts. [86][87][88] Beyond these technical challenges, we are facing a knowledge gap with respect to the evolutionary pathways leading to transformation. Different scenarios can be envisioned that have clearly distinct implications for prediction of transformation ( Figure 2).…”

Section: Challenges and Conceptual Considerationsmentioning

confidence: 99%

Can histologic transformation of follicular lymphoma be predicted and prevented?

Kridel

Sehn

Gascoyne

2017

Blood

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Transformation to aggressive lymphoma is a critical event in the clinical course of follicular lymphoma (FL) patients. Yet, it is a challenge to reliably predict transformation at the time of diagnosis. Understanding the risk of transformation would be useful for guiding and monitoring patients, as well as for evaluating novel treatment strategies that could potentially prevent transformation. Herein, we review the contribution of clinical, pathological, and genetic risk factors to transformation. Patients with multiple clinical high-risk factors are at elevated risk of transformation but we are currently lacking a prognostic index that would specifically address transformation rather than disease progression or overall survival. From the biological standpoint, multiple studies have correlated individual biomarkers with transformation. However, accurate prediction of this event is currently hampered by our limited knowledge of the evolutionary pathways leading to transformation, as well as the scarcity of comprehensive, large-scale studies that assess both the genomic landscape of alterations within tumor cells and the composition of the microenvironment. Liquid biopsies hold great promise for achieving precision medicine. Indeed, mutations detected within circulating tumor DNA may be a better reflection of the inherent intratumoral heterogeneity than the biopsy of a single site. Last, we will assess whether evidence exists in the literature that transformation might be prevented altogether, based on the choice of therapy for FL.

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The Personalization of Therapy: Molecular Profiling Technologies and Their Application

Cited by 6 publications

References 81 publications

Exome Sequencing Identifies Potentially Druggable Mutations in Nasopharyngeal Carcinoma

Exome Sequencing Identifies Potentially Druggable Mutations in Nasopharyngeal Carcinoma

Personalized Medicine and Adverse Drug Reactions: The Experience of An Italian Teaching Hospital

Can histologic transformation of follicular lymphoma be predicted and prevented?

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