#KRAS Mutation Kit
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Future and Growth of Tissue Diagnostics Market by 2030
Tissue Diagnostics Market
The global tissue diagnostics market size was estimated at USD 5.19 billion in 2022 and is expected to grow at a compound annual growth rate (CAGR) of 7.15% from 2023 to 2030.
Tissue diagnostics remains a gold standard for cancer diagnosis as these technologies capture the anatomy of tumors. With rising incidences of cancer, the tissue diagnostics industry witnesses high demand with significant growth opportunities over the forecast period. The impact of COVID-19 on the tissue diagnostics industry has been significant. During the pandemic, there was a slowdown in routine medical procedures, including diagnostic testing, as healthcare resources were redirected toward managing the virus.
Gather more insights about the market drivers, restrains and growth of the Tissue Diagnostics Market
The pandemic led to a temporary decline in the demand for tissue diagnostics products and services. However, as the situation improved and healthcare systems adapted to the new normal, the market began to recover. The need for accurate diagnosis and monitoring of various diseases, including cancer, remained high, driving the demand for tissue diagnostics in the post-pandemic period.
Cancer incidences are increasing dramatically, which has caused a paradigm change in anatomic pathology. This, in turn, is contributing to the clinical pathology field's continued growth. Digitalization of diagnosis methods, increased use of liquid biopsy for cancer detection, and a continuous convergence of anatomical and molecular pathology. The importance of integrated bioinformatics and analyses increases as computational pathology gains momentum. Over the past two decades, the tissue diagnostics industry has changed as more advanced equipment has become available, making life easier for pathologists and physicians.
For instance, in May 2021, to increase the availability of precision medication for lung cancer, QIAGEN released its first FDA-approved tissue companion diagnostic to detect the KRAS G12C mutation in NSCLC tumors. The Rotor-Gene Q MDx instrument, a part of the modular QIAsymphony family of automation solutions, is used with the real-time qualitative PCR kit. This tool builds on QIAGEN's nine years of experience in researching and marketing KRAS CDx tests.
Globally, more than 14 million individuals are diagnosed with cancer each year, and by 2030, that figure is projected to increase to more than 21 million. Major market participants are introducing new cancer diagnosis products. For instance, Roche introduced its innovative BenchMark ULTRA PLUS system for cancer diagnostics in June 2022, enabling prompt, precise patient care. Pathologists can deliver high-quality, time-sensitive results to doctors and patients due to the BenchMark ULTRA PLUS tissue staining system's improved workflow, testing efficiency, and environmentally sustainable features.
Considering the rising worldwide cancer burden, various technologies, and improvements in tissue diagnostics (TDx) will increase pathology efficiency, which is essential for better cancer therapy and diagnosis. For example, Ibex Medical Analytics, the industry pioneer in AI-powered cancer diagnoses, and Alverno Laboratories announced a new deal in March 2023. It aims to expand the implementation of Ibex's Galen suite of Artificial Intelligence solutions to the entire Alverno network across Indiana and Illinois. The deployment comprises AI-powered solutions for cancer diagnosis across numerous tissue types and will help Alverno pathologists in providing the highest quality care for their patients.
A rise in the adoption rate of automated tissue-based diagnostic systems by research institutes enables them to diagnose tumors faster. In January 2023, MilliporeSigma announced its plans to expand its portfolio of antibodies for tissue diagnostics to help improve the classification of gliomas and other tumors in the nervous systems. Such R&D investments will ensure the market continues to grow.
Browse through Grand View Research's Clinical Diagnostics Industry Research Reports.
The global hematologic malignancies market size was valued at USD 67.23 billion in 2023 and is projected to grow at a CAGR of 8.0% from 2024 to 2030.
The global precision diagnostics market size was estimated at USD 15.60 billion in 2023 and is projected to grow at a CAGR of 18.4% from 2024 to 2030.
Key Companies & Market Share Insights
The tissue diagnostics market is fragmented due to the presence of several medium-to-small and large participants in the marketspace. The advent of novel diagnostic models by key players to enhance their technology portfolio has raised competitiveness in the market. For instance, in June 2022, Roche announced the launch of VENTANA DP 600 - the next-generation slide scanner. This high-capacity slide scanner provides the pathology lab with workflow flexibility and ease of use while producing stained histology slides with exceptional image quality from tissue samples. Some prominent players in the global tissue diagnostics market include:
F. Hoffmann-La Roche Ltd.
Abbott Laboratories
Thermo Fisher Scientific Inc.
Siemens
Danaher
bioMérieux SA
QIAGEN
BD
Merck KGaA
GE Healthcare
BioGenex
Cell Signaling Technology, Inc.
Bio SB
DiaGenic ASA
Agilent Technologies
Order a free sample PDF of the Tissue Diagnostics Market Intelligence Study, published by Grand View Research.
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Tissue Diagnostics Market Business Growth, Opportunities and Forecast, 2030
The global tissue diagnostics market size was estimated at USD 5.19 billion in 2022 and is expected to grow at a compound annual growth rate (CAGR) of 7.15% from 2023 to 2030.
Tissue diagnostics remains a gold standard for cancer diagnosis as these technologies capture the anatomy of tumors. With rising incidences of cancer, the tissue diagnostics industry witnesses high demand with significant growth opportunities over the forecast period. The impact of COVID-19 on the tissue diagnostics industry has been significant. During the pandemic, there was a slowdown in routine medical procedures, including diagnostic testing, as healthcare resources were redirected toward managing the virus.
Gather more insights about the market drivers, restrains and growth of the Tissue Diagnostics Market
The pandemic led to a temporary decline in the demand for tissue diagnostics products and services. However, as the situation improved and healthcare systems adapted to the new normal, the market began to recover. The need for accurate diagnosis and monitoring of various diseases, including cancer, remained high, driving the demand for tissue diagnostics in the post-pandemic period.
Cancer incidences are increasing dramatically, which has caused a paradigm change in anatomic pathology. This, in turn, is contributing to the clinical pathology field's continued growth. Digitalization of diagnosis methods, increased use of liquid biopsy for cancer detection, and a continuous convergence of anatomical and molecular pathology. The importance of integrated bioinformatics and analyses increases as computational pathology gains momentum. Over the past two decades, the tissue diagnostics industry has changed as more advanced equipment has become available, making life easier for pathologists and physicians.
For instance, in May 2021, to increase the availability of precision medication for lung cancer, QIAGEN released its first FDA-approved tissue companion diagnostic to detect the KRAS G12C mutation in NSCLC tumors. The Rotor-Gene Q MDx instrument, a part of the modular QIAsymphony family of automation solutions, is used with the real-time qualitative PCR kit. This tool builds on QIAGEN's nine years of experience in researching and marketing KRAS CDx tests.
Globally, more than 14 million individuals are diagnosed with cancer each year, and by 2030, that figure is projected to increase to more than 21 million. Major market participants are introducing new cancer diagnosis products. For instance, Roche introduced its innovative BenchMark ULTRA PLUS system for cancer diagnostics in June 2022, enabling prompt, precise patient care. Pathologists can deliver high-quality, time-sensitive results to doctors and patients due to the BenchMark ULTRA PLUS tissue staining system's improved workflow, testing efficiency, and environmentally sustainable features.
Considering the rising worldwide cancer burden, various technologies, and improvements in tissue diagnostics (TDx) will increase pathology efficiency, which is essential for better cancer therapy and diagnosis. For example, Ibex Medical Analytics, the industry pioneer in AI-powered cancer diagnoses, and Alverno Laboratories announced a new deal in March 2023. It aims to expand the implementation of Ibex's Galen suite of Artificial Intelligence solutions to the entire Alverno network across Indiana and Illinois. The deployment comprises AI-powered solutions for cancer diagnosis across numerous tissue types and will help Alverno pathologists in providing the highest quality care for their patients.
A rise in the adoption rate of automated tissue-based diagnostic systems by research institutes enables them to diagnose tumors faster. In January 2023, MilliporeSigma announced its plans to expand its portfolio of antibodies for tissue diagnostics to help improve the classification of gliomas and other tumors in the nervous systems. Such R&D investments will ensure the market continues to grow.
Tissue Diagnostic Market Segmentation
Grand View Research has segmented the global tissue diagnostics market report based on technology, application, end-use, and region:
Technology Outlook (Revenue, USD Million, 2018 - 2030)
• Immunohistochemistry
o Instruments
o Slide Staining Systems
o Tissue Microarrays
o Tissue Processing Systems
o Slide Scanners
o Other Products
o Consumables
o Antibodies
o Reagents
o Kits
• In Situ Hybridization
o Instruments
o Consumables
o Software
• Primary & Special Staining
• Digital Pathology and Workflow
o Whole Slide Imaging
o Image Analysis Informatics
o Information Management System Storage & Communication
• Anatomic Pathology
o Instruments
o Microtomes & Cryostat Microtomes
o Tissue Processors
o Automatic Strainers
o Other Products
o Consumables
o Reagents & Antibodies
o Probes & Kits
o Others
Application Outlook (Revenue, USD Million, 2018 - 2030)
• Breast Cancer
• Non-small Cell Lung Cancer
• Prostate Cancer
• Gastric Cancer
• Other Cancers
End-use Outlook (Revenue, USD Million, 2018 - 2030)
• Hospitals
• Research Laboratories
• Pharmaceutical Organizations
• Contract Research Organizations (CROs)
Regional Outlook (Revenue, USD Million, 2018 - 2030)
• North America
o U.S.
o Canada
• Europe
o UK
o Germany
o Spain
o France
o Italy
o Denmark
o Sweden
o Norway
• Asia Pacific
o Japan
o China
o India
o South Korea
o Singapore
o Australia
o Thailand
• Latin America
o Brazil
o Mexico
o Argentina
• Middle East and Africa (MEA)
o South Africa
o Saudi Arabia
o UAE
o Kuwait
Browse through Grand View Research's Clinical Diagnostics Industry Research Reports.
• The global hematologic malignancies market size was valued at USD 67.23 billion in 2023 and is projected to grow at a CAGR of 8.0% from 2024 to 2030.
• The global precision diagnostics market size was estimated at USD 15.60 billion in 2023 and is projected to grow at a CAGR of 18.4% from 2024 to 2030.
Key Companies & Market Share Insights
The tissue diagnostics market is fragmented due to the presence of several medium-to-small and large participants in the marketspace. The advent of novel diagnostic models by key players to enhance their technology portfolio has raised competitiveness in the market. For instance, in June 2022, Roche announced the launch of VENTANA DP 600 - the next-generation slide scanner. This high-capacity slide scanner provides the pathology lab with workflow flexibility and ease of use while producing stained histology slides with exceptional image quality from tissue samples. Some prominent players in the global tissue diagnostics market include:
• F. Hoffmann-La Roche Ltd.
• Abbott Laboratories
• Thermo Fisher Scientific Inc.
• Siemens
• Danaher
• bioMérieux SA
• QIAGEN
• BD
• Merck KGaA
• GE Healthcare
• BioGenex
• Cell Signaling Technology, Inc.
• Bio SB
• DiaGenic ASA
• Agilent Technologies
Order a free sample PDF of the Tissue Diagnostics Market Intelligence Study, published by Grand View Research.
#Tissue Diagnostics Market#Tissue Diagnostics Industry#Tissue Diagnostics Market size#Tissue Diagnostics Market share#Tissue Diagnostics Market analysis
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#BCR ABL PCR Kit#bcr abl quantitative pcr kit#JAK-2 PCR Kit#KRAS Mutation Kit#EGFR Mutation Kit#Factor V PCR Kit#Factor II PCR Kit#HLA-B27 PCR Kit#TB PCR Kit#Rifampicin Resistant MTB Kit#HBV Viral Load Kit#HIV Viral Load Kit#Dengue RT PCR Kit
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#miRNA-1290 Promotes Aggressiveness in Pancreatic Ductal Adenocarcinoma by Targeting IKK1.
Related Articles #miRNA-1290 Promotes Aggressiveness in Pancreatic Ductal Adenocarcinoma by Targeting IKK1. Cell Physiol Biochem. 2018;51(2):711-728 Authors: Ta N, Huang X, Zheng K, Zhang Y, Gao Y, Deng L, Zhang B, Jiang H, Zheng J Abstract BACKGROUND/AIMS: Micro#RNAs (#miRNAs) are a group of non-coding #RNAs that play diverse roles in pancreatic carcinogenesis. In pancreatic ductal adenocarcinoma (PDAC), NF-kB is constitutively activated in most patients and is linked to a mutation in KRAS via IkB kinase complex 1 (IKK1, also known as IKKa). We investigated the link between PDAC aggressiveness and miR-1290. METHODS: We used miRCURYTM LNA Array and in situ hybridization to investigate candidate #miRNAs and validated the findings with PCR. The malignant behavior of cell lines was assessed with Cell Counting Kit-8, colony formation, and Transwell assays. A dual-luciferase reporter assay was used to evaluate the interaction between miR-1290 and IKK1. Protein expression was observed by western blotting. RESULTS: In this study, 36 #miRNAs were dysregulated in high-grade pancreatic intraepithelial neoplasia (PanIN) and PDAC tissues compared with low-grade PanIN tissues. The area under the curve values of miR-1290 and miR-31-5p were 0.829 and 0.848, respectively (95% confidence interval, 0.722-0.936 and 0.749-0.948, both P
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Cancers, Vol. 11, Pages 266: Identification of Novel HLA Class II-Restricted Neoantigens Derived from Driver Mutations
Cancers, Vol. 11, Pages 266: Identification of Novel HLA Class II-Restricted Neoantigens Derived from Driver Mutations
Cancers doi: 10.3390/cancers11020266
Authors: Susumu Iiizumi Junya Ohtake Naoko Murakami Taku Kouro Mamoru Kawahara Fumiko Isoda Hiroshi Hamana Hiroyuki Kishi Norihiro Nakamura Tetsuro Sasada
Neoantigens derived from tumor-specific genetic mutations might be suitable targets for cancer immunotherapy because of their high immunogenicity. In the current study, we evaluated the immunogenicity of 10 driver mutations that are frequently expressed in various cancers using peripheral blood mononuclear cells from healthy donors (n = 25). Of the 10 synthetic peptides (27-mer) derived from these mutations, the six peptides from KRAS-G12D, KRAS-G12R, KRAS-G13D, NRAS-Q61R, PIK3CA-H1047R, and C-Kit-D816V induced T cell responses, suggesting that frequent driver mutations are not always less immunogenic. In particular, immune responses to PIK3CA-H1047R, C-Kit-D816V, KRAS-G13D, and NRAS-Q61R were observed in more than 10% of the donors. All six peptides induced human leukocyte antigen (HLA) class II-restricted CD4+ T cell responses; notably, PIK3CA-H1047R contained at least two different CD4+ T cell epitopes restricted to different HLA class II alleles. In addition, PIK3CA-H1047R and C-Kit-D816V induced antigen-specific CD8+ T cells as well, indicating that they might contain both HLA class I- and class II-restricted epitopes. Since the identified neoantigens might be shared by patients with various types of cancers and are not easily lost due to immune escape, they have the potential to be promising off-the-shelf cancer immunotherapy targets in patients with the corresponding mutations.
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#BCR ABL PCR Kit#bcr abl quantitative pcr kit#JAK-2 PCR Kit#KRAS Mutation Kit#EGFR Mutation Kit#Factor V PCR Kit#Factor II PCR Kit#HLA-B27 PCR Kit#TB PCR Kit#Rifampicin Resistant MTB Kit#HBV Viral Load Kit
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#BCR ABL PCR Kit#bcr abl quantitative pcr kit#KRAS Mutation Kit#EGFR Mutation Kit#Factor V PCR Kit#Factor II PCR Kit#HLA-B27 PCR Kit#TB PCR Kit
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#HCV Viral Load Kit#H1N1 PCR Kit#PML RARA RT PCR Kit#MTB PCR Kit#MDR TB Kit#HCV Genotyping Kit#HPV 16 & 18 Detection Kit#Chikungunya RT PCR Kit#Dengue RT PCR Kit#HIV Viral Load Kit#HBV Viral Load Kit#Rifampicin Resistant MTB Kit#TB PCR Kit#HLA-B27 PCR Kit#Factor II PCR Kit#Factor V PCR Kit#EGFR Mutation Kit#KRAS Mutation Kit#JAK-2 PCR Kit#bcr abl quantitative pcr kit#BCR ABL PCR Kit
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#BCR ABL PCR Kit#bcr abl quantitative pcr kit#JAK-2 PCR Kit#KRAS Mutation Kit#EGFR Mutation Kit#Factor V PCR Kit#Factor II PCR Kit#HLA-B27 PCR Kit#HBV Viral Load Kit#HIV Viral Load Kit#Dengue RT PCR Kit#HPV 16 & 18 Detection Kit#HCV Genotyping Kit#MDR TB Kit#PML RARA RT PCR Kit
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#BCR ABL PCR Kit\#bcr abl quantitative pcr kit#JAK-2 PCR Kit#KRAS Mutation Kit#EGFR Mutation Kit#Factor V PCR Kit#Factor II PCR Kit#HLA-B27 PCR Kit#TB PCR Kit#Rifampicin Resistant MTB Kit#HBV Viral Load Kit#HIV Viral Load Kit#Dengue RT PCR Kit#Chikungunya RT PCR Kit#HPV 16 & 18 Detection Kit#HPV High Risk Detection Kit#HCV Genotyping Kit#MDR TB Kit#MTB PCR Kit#PML RARA RT PCR Kit#H1N1 PCR Kit#HCV Viral Load Kit
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The gene mutational discrepancies between primary and paired metastatic colorectal carcinoma detected by next-generation sequencing
Abstract
Purpose
To better understand the gene mutational status and heterogeneity between primary and metastatic CRC (mCRC) using a sensitive sequencing method.
Methods
The mutational status of EGFR, KRAS, NRAS, PIK3CA, ERBB2, BRAF, KIT, and PDGFRA was analyzed in 65 patients, with 147 samples of primary and paired live or lung metastatic CRC, using next-generation sequencing (NGS), quantitative RT-PCR (qPCR), and Sanger sequencing.
Results
Fifteen cases (15/22, 68.2%) of lung mCRC and thirteen cases (13/20, 65%) of liver mCRC harboured the same mutation profiles of KRAS, NRAS, or BRAF in the primary lesions. To all detected genes, 11 cases (11/22, 50%) of lung mCRC and 11 cases (11/20, 55%) of liver mCRC showed different mutational genes in the primary tumours. KRAS and BRAF mutations were more frequent in lung metastatic lesions (p = 0.004 and 0.003, respectively). The gene mutations in KRAS, NRAS, BRAF, and PIK3CA in the lung metastatic sites were more frequent than those in the liver metastatic sites (86.7 vs. 44%, respectively, p = 0.000). Some new mutations were not covered in the qPCR ranges but were detected by NGS.
Conclusion
The study demonstrated that the discordance of gene mutational status between paired primary and metastatic tumours is rather high when detected by NGS. Evaluating the mutational status of both the primary and metastatic tumours should be considered in clinical mutation testing.
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Resistance Mechanisms to Targeted Therapies in ROS1+ and ALK+ Non-small Cell Lung Cancer
Purpose: Despite initial benefit from tyrosine kinase inhibitors (TKIs), patients with advanced non–small cell lung cancer (NSCLC) harboring ALK (ALK+) and ROS1 (ROS1+) gene fusions ultimately progress. Here, we report on the potential resistance mechanisms in a series of patients with ALK+ and ROS1+ NSCLC progressing on different types and/or lines of ROS1/ALK–targeted therapy.
Experimental Design: We used a combination of next-generation sequencing (NGS), multiplex mutation assay, direct DNA sequencing, RT-PCR, and FISH to identify fusion variants/partners and copy-number gain (CNG), kinase domain mutations (KDM), and copy-number variations (CNVs) in other cancer-related genes. We performed testing on 12 ROS1+ and 43 ALK+ patients.
Results: One of 12 ROS1+ (8%) and 15 of 43 (35%) ALK+ patients harbored KDM. In the ROS1+ cohort, we identified KIT and β-catenin mutations and HER2-mediated bypass signaling as non-ROS1–dominant resistance mechanisms. In the ALK+ cohort, we identified a novel NRG1 gene fusion, a RET fusion, 2 EGFR, and 3 KRAS mutations, as well as mutations in IDH1, RIT1, NOTCH, and NF1. In addition, we identified CNV in multiple proto-oncogenes genes including PDGFRA, KIT, KDR, GNAS, K/HRAS, RET, NTRK1, MAP2K1, and others.
Conclusions: We identified a putative TKI resistance mechanism in six of 12 (50%) ROS1+ patients and 37 of 43 (86%) ALK+ patients. Our data suggest that a focus on KDMs will miss most resistance mechanisms; broader gene testing strategies and functional validation is warranted to devise new therapeutic strategies for drug resistance. Clin Cancer Res; 24(14); 3334–47. ©2018 AACR.
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Value of a molecular screening program to support clinical trial enrollment in Asian cancer patients: The Integrated Molecular Analysis of Cancer (IMAC) Study
Abstract
The value of precision oncology initiatives in Asian contexts remains unresolved. Here we review the institutional implementation of prospective molecular screening to facilitate accrual of patients into biomarker-driven clinical trials, and to explore the mutational landscape of advanced tumors occurring in a prospective cohort of Asian patients (n = 396) with diverse cancer types. Next-generation sequencing (NGS) and routine clinicopathological assays such as immunohistochemistry, copy number analysis, and in situ hybridization tests were performed on tumor samples. Actionable biomarker results were used to identify eligibility for early-phase, biomarker-driven clinical trials. Overall, NGS was successful in 365 of 396 patients (92%), achieving a mean depth of 1,943× and coverage uniformity of 96%. The median turnaround time from sample receipt to return of genomic results was 26.0 days (IQR, 19.0-39.0 days). Reportable mutations were found in 300 of 365 patients (82%). Ninety-one percent of patients at study enrollment indicated consent to receive incidental findings and willingness to undergo genetic counseling if required. The most commonly mutated oncogenes included KRAS (19%), PIK3CA (16%), EGFR (5%), BRAF (3%), and KIT (3%); while the most frequently mutated tumor suppressor genes included TP53 (40%), SMARCB1 (12%), APC (8%), PTEN (6%), and SMAD4 (5%). Among 23 patients enrolled in genotype-matched trials, median progression-free survival was 2.9 months (IQR, 1.5 to 4.0 months). Nine of 20 evaluable patients (45%; 95% CI, 23.1% to 68.5%) derived clinical benefit, including 3 partial responses and 6 with stable disease lasting ≥ 8 weeks. This article is protected by copyright. All rights reserved.
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Use of the QIAGEN GeneReader NGS system for detection of KRAS mutations, validated by the QIAGEN Therascreen PCR kit and alternative NGS platform
Abstract
Background
The detection of somatic mutations in primary tumors is critical for the understanding of cancer evolution and targeting therapy. Multiple technologies have been developed to enable the detection of such mutations. Next generation sequencing (NGS) is a new platform that is gradually becoming the technology of choice for genotyping cancer samples, owing to its ability to simultaneously interrogate many genomic loci at massively high efficiency and increasingly lower cost. However, multiple barriers still exist for its broader adoption in clinical research practice, such as fragmented workflow and complex bioinformatics analysis and interpretation.
Methods
We performed validation of the QIAGEN GeneReader NGS System using the QIAact Actionable Insights Tumor Panel, focusing on clinically meaningful mutations by using DNA extracted from formalin-fixed paraffin-embedded (FFPE) colorectal tissue with known KRAS mutations. The performance of the GeneReader was evaluated and compared to data generated from alternative technologies (PCR and pyrosequencing) as well as an alternative NGS platform. The results were further confirmed with Sanger sequencing.
Results
The data generated from the GeneReader achieved 100% concordance with reference technologies. Furthermore, the GeneReader workflow provides a truly integrated workflow, eliminating artifacts resulting from routine sample preparation; and providing up-to-date interpretation of test results.
Conclusion
The GeneReader NGS system offers an effective and efficient method to identify somatic (KRAS) cancer mutations.
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Genomic Profiling of Large-Cell Neuroendocrine Carcinoma of the Lung
Purpose: Although large-cell neuroendocrine carcinoma (LCNEC) of the lung shares many clinical characteristics with small-cell lung cancer (SCLC), little is known about its molecular features. We analyzed lung LCNECs to identify biologically relevant genomic alterations.
Experimental Design: We performed targeted capture sequencing of all the coding exons of 244 cancer-related genes on 78 LCNEC samples [65 surgically resected cases, including 10 LCNECs combined with non–small cell lung cancer (NSCLC) types analyzed separately, and biopsies of 13 advanced cases]. Frequencies of genetic alterations were compared with those of 141 SCLCs (50 surgically resected cases and biopsies of 91 advanced cases).
Results: We found a relatively high prevalence of inactivating mutations in TP53 (71%) and RB1 (26%), but the mutation frequency in RB1 was lower than that in SCLCs (40%, P = 0.039). In addition, genetic alterations in the PI3K/AKT/mTOR pathway were detected in 12 (15%) of the tumors: PIK3CA 3%, PTEN 4%, AKT2 4%, RICTOR 5%, and mTOR 1%. Other activating alterations were detected in KRAS (6%), FGFR1 (5%), KIT (4%), ERBB2 (4%), HRAS (1%), and EGFR (1%). Five of 10 cases of LCNECs combined with NSCLCs harbored previously reported driver gene alterations, all of which were shared between the two components. The median concordance rate of candidate somatic mutations between the two components was 71% (range, 60%–100%).
Conclusions: LCNECs have a similar genomic profile to SCLC, including promising therapeutic targets, such as the PI3K/AKT/mTOR pathway and other gene alterations. Sequencing-based molecular profiling is warranted in LCNEC for targeted therapies. Clin Cancer Res; 23(3); 757–65. ©2016 AACR.
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Retrospective study of RAS/PIK3CA/BRAF tumor mutations as predictors of response to first-line chemotherapy with bevacizumab in metastatic colorectal cancer patients
Abstract
Background
After analysis of minor RAS mutations (KRAS exon 3, 4/NRAS) in the FIRE-3 and PRIME studies, an expanded range of RAS mutations were established as a negative predictive marker for the efficacy of anti-EGFR antibody treatment. BRAF and PIK3CA mutations may be candidate biomarkers for anti-EGFR targeted therapies. However, it remains unknown whether RAS/PIK3CA/BRAF tumor mutations can predict the efficacy of bevacizumab in metastatic colorectal cancer. We assessed whether selection according to RAS/PIK3CA/BRAF mutational status could be beneficial for patients treated with bevacizumab as first-line treatment for metastatic colorectal cancer.
Methods
Of the 1001 consecutive colorectal cancer patients examined for RAS, PIK3CA, and BRAF tumor mutations using a multiplex kit (Luminex®), we studied 90 patients who received combination chemotherapy with bevacizumab as first-line treatment for metastatic colorectal cancer. The objective response rate (ORR) and progression-free survival (PFS) were evaluated according to mutational status.
Results
The ORR was higher among patients with wild-type tumors (64.3%) compared to those with tumors that were only wild type with respect to KRAS exon 2 (54.8%), and the differences in ORR between patients with wild-type and mutant-type tumors were greater when considering only KRAS exon 2 mutations (6.8%) rather than RAS/PIK3CA/BRAF mutations (18.4%). There were no statistically significant differences in ORR or PFS between all wild-type tumors and tumors carrying any of the mutations. Multivariate analysis revealed that liver metastasis and RAS and BRAF mutations were independent negative factors for disease progression after first-line treatment with bevacizumab.
Conclusions
Patient selection according to RAS/PIK3CA/BRAF mutations could help select patients who will achieve a better response to bevacizumab treatment. We found no clinical benefit of restricting combination therapy with bevacizumab for metastatic colorectal cancer patients with EGFR-wild type tumors.
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