Integrated DNA, RNA and protein analyses for a better treatment of cancer patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23099-e23099
Author(s):  
Jean-Francois Laes ◽  
Francois Cesbron ◽  
Gregori Ghitti
Keyword(s):  
Cancer Treatment ◽  
Precision Medicine ◽  
Gene Promoter ◽  
Molecular Profiling ◽  
Cancer Therapies ◽  
Diagnostic Service ◽  
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Formalin Fixed Paraffin Embedded ◽  
Targeted Cancer Therapies ◽  
Treatment Plans

e23099 Background: Advances in the molecular profiling of tumours, together with the expanding portfolio of targeted cancer therapies have established the terrain on which personalised cancer treatment can be conducted. This expanding area of precision medicine has the potential to be offered as a routine cancer-diagnostic service. Methods: We evaluated two molecular-profiling approaches : next-generation sequencing (NGS) and a group of several assays, termed Package Plus (PP), which have been primarily designed at identifying specific clinically-relevant alterations including protein expression/activation (by immunohistochemistry), and gene-promoter methylation, gene translocations and microsatellite instability (by PCR). The molecular profiling was conducted as diagnostic service for practising oncologists, who provided formalin-fixed paraffin-embedded tumour samples (for NGS and PP) and blood samples for circulating tumour DNA (for NGS only). A subset of oncologists who received the molecular profiling results and treatment advice was then surveyed to assess whether and how the results affected their treatment plans. Results: 980 samples from 16 different cancer types were received, out of which 914 (93%) were of sufficient quality to be included in this study. Clinically-relevant (actionable) alterations that provided treatment advice were identified for the large majority (841/914; 92%) of patients using the combination of NGS and PP data, but only for a minority of (247/912; 27%) of patients using NGS data alone. Treatment advice was adhered to by the oncologist in the majority (60%) of surveyed cases, and in the cases where the advice was not followed, reasons most often cited were treatment unavailability or cost. Conclusions: Our study demonstrates the utility of a precision-medicine service based on supervised tests (protein and RNA) in combination with NGS (DNA) profiling methods for advising oncologists on appropriate cancer-treatment plans.

scholarly journals MS3-1 IMPLEMENTATION OF GENE PANEL TESTING USING NEXT-GENERATION SEQUENCING

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii3-ii3
Author(s):  
Kazuko Sakai
Keyword(s):  
Cancer Treatment ◽  
Gene Mutation ◽  
Diagnostic Testing ◽  
Gene Panel ◽  
Panel Testing ◽  
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Gene Panel Testing ◽  
Companion Diagnostic ◽  
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Formalin Fixed

Abstract The advance of next-generation sequencers (NGS) has dramatically improved the performance of genomic analysis of clinical samples in cancer precision medicine. The practical use of gene panel testing for clinical applications has begun in Japan. At present, “OncomineTM Dx Target Test” is listed as a companion diagnostic system using NGS, and “FoundationOne CDx Cancer Genomic Profile” and “OncoGuide™ NCC Oncopanel System” are listed as gene panel testing under insurance coverage. Formalin-fixed paraffin-embedded specimen have been routinely used for molecular diagnosis testing, therefore quality control such as formalin fixation time and tumor contents is important to ensure validity of diagnostic results. In this presentation, the issue to obtain evaluable results of gene panel testing using formalin-fixed paraffin-embedded specimen will be discussed. Due to evolution of detection technologies, we can detect gene mutation with high sensitivity. Detection of gene mutation in circulating tumor DNA is feasible approach for diagnostic testing in cancer treatment. Liquid biopsy has been approved as a companion diagnostic testing to detect EGFR mutations in NSCLC. Examples of the clinical utility of plasma testing in cancer treatment will be presented.

Feasibility of molecular profiling based assignment of cancer treatment (MPACT): A randomized NCI precision medicine study.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 2539-2539 ◽  
Author(s):  
Alice P. Chen ◽  
Mickey Williams ◽  
Shivaani Kummar ◽  
Chih-Jian Lih ◽  
Vivekananda Datta ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Precision Medicine ◽  
Molecular Profiling

scholarly journals An evidence-based network approach to recommending targeted cancer therapies

2019 ◽  
Author(s):  
Jayaram Kancherla ◽  
Shruti Rao ◽  
Krithika Bhuvaneshwar ◽  
Rebecca B. Riggins ◽  
Robert A. Beckman ◽  
...  
Keyword(s):  
Molecular Profiling ◽  
Evidence Based ◽  
Cancer Type ◽  
Biological Pathway ◽  
Cancer Therapies ◽  
Network Approach ◽  
Molecular Alterations ◽  
Sources Of Knowledge ◽  
Targeted Cancer Therapies ◽  
User Friendly

AbstractIn this work, we introduce CDGnet, an evidence-based network approach for recommending targeted cancer therapies, available as a user-friendly informatics tool. Our approach can be used to expand the range of options of targeted therapies for cancer patients who undergo molecular profiling. It considers biological pathway information specifically by looking at downstream targets of oncogenes and is personalized for individual patients via the user-inputted molecular alterations and cancer type. CDGnet integrates disparate sources of knowledge and provides results in a number of easily-accessible and usable forms, while separating targeted cancer therapies into categories in an evidence-based manner.

scholarly journals Deamination Effects in Formalin-Fixed, Paraffin-Embedded Tissue Samples in the Era of Precision Medicine

2017 ◽  
Vol 19 (1) ◽  
pp. 137-146 ◽  
Author(s):  
Seokhwi Kim ◽  
Charny Park ◽  
Yongick Ji ◽  
Deok G. Kim ◽  
Hyunsik Bae ◽  
...  
Keyword(s):  
Precision Medicine ◽  
Tissue Samples ◽  
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Formalin Fixed Paraffin Embedded ◽  
Formalin Fixed

Integrating phosphoproteomics into kinase-targeted cancer therapies in precision medicine

2019 ◽  
Vol 191 ◽  
pp. 68-79 ◽  
Author(s):  
Xiaomo Wu ◽  
Xiaohua Xing ◽  
Djameel Dowlut ◽  
Yongyi Zeng ◽  
Jingfeng Liu ◽  
...  
Keyword(s):  
Precision Medicine ◽  
Cancer Therapies ◽  
Targeted Cancer Therapies

Unknown primary cancer (UPC): Accuracy of tissue of origin prediction by molecular profiling

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11070-11070
Author(s):  
F. A. Greco ◽  
D. R. Spigel ◽  
D. A. Yardley ◽  
M. Erlander ◽  
X. Ma ◽  
...  
Keyword(s):  
Molecular Profiling ◽  
Primary Site ◽  
Unknown Primary ◽  
Rt Pcr ◽  
Pcr Assay ◽  
Arch Pathol ◽  
Pcr Diagnosis ◽  
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Diagnostic Biopsy ◽  
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11070 Background: Molecular profiling may be useful to identify the primary site and direct therapy for patients (pts) with UPC. Since most UPC pts never have a primary site identified, the accuracy of molecular profiling diagnoses are difficult to verify. We identified a group of UPC pts who had a primary site subsequently identified during their clinical course, and performed a 92-gene real time polymerase chain reaction (RT-PCR) assay (Arch Pathol Lab Med 130:465, 2006) on tissue from the initial diagnostic biopsy. We then compared the RT-PCR diagnosis with the subsequent clinical diagnosis. Methods: 38 of 501 UPC pts (7%) seen between 2000 and 2008 had their primary tumor subsequently identified during life. 24 of the 38 pts had tissue biopsies (excluding FNA cytology) and are the subject of this study. The RT-PCR assay was performed on unstained slides from the formalin-fixed, paraffin-embedded (FFPE) initial diagnostic biopsy, and the assay predictions were compared to the actual primary sites (found later). No clinical or pathologic data (other than sex, biopsy site, and 1 H&E stained slide) were used in the prediction of the primary site. Results: 16 of 24 assays were successful (8 had no tumor or RNA in the material). 11 of 16 predictions of the site of origin (68%) were correct, corresponding to the actual primary sites found 3–58 months (median 8.5 months) after the initial diagnosis of UPC. Primary sites correctly identified included breast 2, ovary/peritoneal 4, NSCLC 1, colorectal 2, gastric 1, melanoma 1. 3 predictions were inaccurate (colorectal, testicular, sarcoma) in patients with gastroesophageal, pancreas and NSCLC, respectively. 2 assays were unclassifiable. Conclusions: RT-PCR performed on FFPE initial diagnostic tissue was accurate in predicting the primary site of origin in 11 of 16 pts with UPC who eventually had their primary site identified clinically. These data provide a direct validation of the reliability of this RT-PCR assay in predicting the primary site in pts with UPC. When used in concert with clinical features and IHC stains, molecular profiling may provide the basis for more successful site-directed therapy for many of these pts. Prospective studies of RT-PCR in UPC are ongoing. [Table: see text]

Identifying Mcl-1 protein dependencies using dimerization-specific antibody biomarker for predicting response to targeted apoptosis inducing therapies.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 7038-7038
Author(s):  
Michael H. Cardone ◽  
Sae Rin Jean ◽  
Bahriye Karakas ◽  
Sonia Kumar ◽  
Max Narovlyansky ◽  
...  
Keyword(s):  
Leukemia Cell ◽  
Predictive Biomarker ◽  
Response To Therapy ◽  
Cancer Therapies ◽  
Cancer Treatments ◽  
Protein Levels ◽  
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Mimetic Peptides ◽  
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Bh3 Mimetic

7038 Background: The anti-apoptotic Bcl-2 family proteins facilitate pro-survival and resistance to anti-cancer therapies. Measuring the function of these proteins has shown utility in predicting response to therapy. A method that expands the principle of BH3 profiling to solid tumors is presented. Measuring the occurrence of heterodimers of Myeloid Leukemia Cell Differentiation Protein (Mcl-1), and pro-apoptotic binding protein Bim is an indicator of cancer cell apoptotic priming state. The readout of Mcl-1 containing complex-specific biomarkers can identify survival dependencies in cancer cells potentially providing clinical utility in guiding cancer treatments. Methods: Engineered immunogens that recapitulate conformation-specific epitopes induced during binding of the Mcl-1/Bim protein complex were used to generate. monoclonal antibodies. One Heterodimer Specific Mcl-1 Bim (HsMcB) was chosen. The selective binding was confirmed using ELISA, fluorescence polarization, immunofluorescence microscopy and flow cytometry in Bim or Mcl-1 knockdown cells, and by immunohistochemistry in formalin-fixed paraffin-embedded patient tissue. Correlation of HsMcB measurements to BH3 profiling readouts from the Mcl-1 restricted Noxa peptide was explored. Results: HsMcB signal depends on both Mcl-1 and Bim protein levels. The ratio of the HsMcB to unbound protein (Mcl-1) signal ([HsMcB]/[Mcl-1]) was measured. Disruption of the complexes by BH3 mimetics targeted to Mcl-1 and depletion of Mcl-1 level using CDK9 inhibitors diminished the [HsMcB]/[Mcl-1] readout. We see correlations between these readouts and BH3 mimetic peptides readouts from the Mcl-1 specific Noxa and MS1 BH3 mimetic peptides in AML patient samples that have been treated with Mcl-1 inhibitors. Conclusions: Mcl-1 dependence is a predictive biomarker for venetoclax resistance and for response to Mcl-1 targeted therapies. Flow cytometric and IHC based measurements of a heterodimer complex offer a direct and simpler approach that harbors potential for use in clinical settings. Additional antibodies targeting Mcl-1/Bak and Mcl-1 Noxa complexes are being tested.

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