Mocht u kanker-actueel de moeite waard vinden en ons willen ondersteunen om kanker-actueel online te houden dan kunt u ons machtigen voor een periodieke donatie via donaties 
Of doneer al of niet anoniem op - rekeningnummer NL79 RABO 0372931138 t.n.v. Stichting Gezondheid Actueel in Terneuzen. Onze IBANcode is NL79 RABO 0372 9311 38   

Elk bedrag is welkom. En we zijn een ANBI instelling dus uw donatie of gift is in principe aftrekbaar voor de belasting. 

En als donateur kunt u ook korting krijgen bij verschillende bedrijven

We kunnen u eventueel in contact brengen met een oncoloog en met een Nederlandse patholoog die u eventueel verder kunnen helpen bij het aanvragen van een Carisrapport. Al zal uw behandelend arts daar toch ook mee in moeten stemmen in principe om de aanbevelingen uit een rapport dan ook te volgen. Maar dat kunt u ook bespreken met de bemiddelende artsen hoe dat te doen. Op de website van Caris Lifesciences staan hier publicaties van de laatste 5 jaar met moleculaire testen. 

18 juni 2019: Bron: Whiley online library

In een uitstekend en gedetailleerd artikel beschrijven een groep van bekende wetenschappers en artsen wat de huidige staat is van moleculair testen. En wat dat betekent voor het behandelen van kanker met solide tumoren. Onafhankelijk van de primaire tumordiagnose. Aan bod komen de verschillen en soms ook overeenkomsten tussen RNA mutaties, DNA mutaties en eiwitexpressie. 

Een aantal al bekende mutaties gekoppeld aan de door FDA en EMU geregistreerde medicijnen die horen bij bepaalde mutaties of eiwitexpressie is deze grafiek. En bedenk dat eigenlijk dit los staat van de primaire tumordiagnose al wordt daar nog veel te weinig mee gedaan, maar dit gaat ongetwijfeld veranderen. Dat een medicijn voor BRCA gerelateerde vormen van kanker niet alleen maar voor borstkanker of eierstokkanker gaat gebruikt worden maar ook voor andere vormen van kanker met BRCA mutaties. En zo zijn er veel meer voorbeelden te noemen, zoals HER2 expressie, EGFR mutaties, MSI instabiel enz. , maar zie deze grafiek:

Table 7. Broadening Molecular Profiling Boundaries—Biomarker‐Targeted Therapy Matches

TARGETED MUTATIONDRUG
NCI‐MATCH trial: NCT02465060aNCI‐MATCH trial: Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma. Matches are as listed on ClinicalTrials.gov/ct2/show/NCT02465060. Accessed February 6, 2019. After patient tumor molecular testing on a main screening protocol, those with actionable mutations are assigned to 1 of 35 treatment subprotocols.
EGFR activating mutation Afatinib
HER2 activating mutation Afatinib
BRCA1 or BRCA2 mutations Adavosertib (AZD1775)
FGFR pathway aberrations AZD4547
NRAS12, NRAS13, NRAS61 mutation Binimetinib
AKT mutation Capivasertib (AZD 5363)
PIK3CA mutation Copanlisib
PTEN mutation Copanlisib
PTEN loss Copanlisib
MET amplification Crizotinib
MET exon 14 deletion Crizotinib
ALK translocation Crizotinib
ROS1 translocation or inversion Crizotinib
BRAF V600E/V600R/V600K/V600D mutation Dabrafenib + trametinib
DDR2 S768R, I638F, or L239R mutation Dasatinib
NF2 inactivating mutation Defactinib
PTEN mutation or deletion and PTEN expression GSK2636771 (PI3Kβ inhibitor)
PTEN loss GSK2636771 (PI3Kβ inhibitor)
FGFR mutation or fusion Erdafitinib
FGFR amplification Erdafitinib
NTRK1, NTRK2, NRTK3 gene fusions Larotrectinib (LOXO‐101)
Loss of MLH1 or MSH2 (by IHC) Nivolumab
EGFR T790M or rare activating mutation Osimertinib
CCND1, CCND2, CCND3 amplification & Rb expression Palbociclib
CDK4 or CDK6 amplification and Rb protein Palbociclib
HER2 amplification ≥7 copy numbers Pertuzumab + trastuzumab
TSC1 or TSC2 mutation Sapanisertib
mTOR mutation Sapanisertib
cKIT exon 9, 11, 13, or 14 mutation Sunitinib
PIK3CA mutation Taselisib
GNAQ/GNA11 mutation Trametinib
BRAF fusion or BRAF non‐V600 mutation Trametinib
NF1 mutation Trametinib
HER2 amplification Trastuzumab emtansine
SMO/PTCH1 mutation Vismodegib
TAPUR trial: NCT02693535bThe American Society of Clinical Oncology's TAPUR trial: Testing the Use of US Food and Drug Administration‐Approved Drugs That Target a Specific Abnormality in a Tumor Gene in People With Advanced Stage Cancer. Matches are as listed on clinicaltrials.gov/ct2/show/NCT02693535. Accessed February 6, 2019.
VEGFR mutation, amplification or overexpression Axitinib
Bcr‐abl, SRC, LYN, LCK mutations Bosutinib
ALK, ROS1, MET mutations Crizotinib
KRAS, NRAS, and BRAF (all wild type) Cetuximab
Bcr‐abl, SRC, KIT, PDGFRB, EPHA2, FYN, LCK, YES1 mutations Dasatinib
BRCA1/BRCA2 inactivating mutations; ATM mutations/deletions Olaparib
MSI‐high, high TML, and others Nivolumab and ipilimumab
CDKN2A, CDK4, CDK6 amplifications Palbociclib
POLE/POLD1 mutations; high TML Pembrolizumab
VEGFR1, VEGFR2, VEGFR3, PDGFRB, RET, KIT, RAF‐1, BRAF mutations/amplifications Regorafenib
PDGFR, VEGFR, CSF1R Sunitinib
mTOR, TSC mutations Temsirolimus
ERBB2 amplifications Trastuzumab and pertuzumab
BRAF V600E mutations Vemurafenib and cobimetinib

Het gaat me te ver om alles te vertalen want het is behoorlijk medisch technisch al leest het in sommige delen van het artikel best makkelijk, in ieder geval voor mij. Zo worden de methodes van moleculaire testen ook beschreven in wat de verschillen zijn en overeenkomsten en waar ze toe dienen in relatie tot een behandeling van kanker.

DNA and RNA

  • Polymerase chain reaction (PCR) is used to amplify and detect DNA and RNA sequences. Standard PCR involves the amplification of one or more copies of a chosen DNA sequence to produce millions of copies and enable detection and analysis. Reverse transcription PCR converts RNA templates into complementary DNA for molecular analysis.
  • In situ hybridization (ISH) localizes and determines a specific DNA or RNA sequence in a tissue section (in situ) or in circulating tumor cells using a labeled complementary DNA, RNA, or modified nucleic acid strand probe. This technique detects gene deletions, amplifications, translocations, and fusions. Gene fusions commonly occur in epithelial cancers as a result of genomic rearrangements or abnormal mRNA processing. ISH techniques include chromogenic ISH and fluorescence in situ hybridization (FISH).
    • Chromogenic in situ hybridization (CISH) uses brightfield microscopes for label detection.
    • FISH uses fluorescence microscopes for label detection.
  • Sanger sequencing examines strands of DNA to identify mutations by analyzing long, contiguous sequencing reads. This DNA sequencing takes place according to the selective incorporation of chain‐terminating dideoxynucleotides by DNA polymerase during in vitro DNA replication. This was the primary sequencing method used for well over 20 years and, although it is still widely used, next‐generation sequencing (NGS) is now preferred for multigene/variant assessment.
  • NGS is a high‐throughput technique that rapidly examines and more broadly detects DNA mutations (often used for circulating tumor DNA), copy number variations (CNVs), and gene fusions (using an RNA sequencing panel) across the genome. NGS can be performed on a range of cancer types using blood, solid tissue, and bone marrow samples. Precise tissue collection and workup are necessary for accurate results. Laboratory regulatory agencies constantly provide updated guidance documents pertaining to the design, development, and use of NGS‐based tests, recognizing the importance of NGS in cancer diagnostics and therapeutics.
  • Pyrosequencing detects and quantifies mutations, methylation, etc, through sequencing by synthesis—a method that performs DNA sequencing by detecting the nucleotide that is incorporated by DNA polymerase.
  • Fragment analysis detects changes in DNA (eg, the length of a specific DNA sequence) or RNA to indicate the presence or absence of an inserted or deleted genomic sequence.

Protein

  • Immunohistochemistry (IHC) uses the principles of antibody binding to proteins to determine the levels of protein expression in tissue samples. Tumor‐related proteins of interest can include tumor‐specific antigens, protein products of oncogenes and tumor suppressor genes, tumor cell proliferation markers, and enzymes. 

Maar leest u verder het artikel door op de volgende link te klikken: 

Molecular Profiling Assays and Why Physician Oncologists and Pathologists Should Be Familiar With Them

Hier het abstract van dit artikel met alle genoemde wetenschappers en artsen die hieraan hebben meegewerkt en indeling van het artikel: 

The current state of molecular testing in the treatment of patients with solid tumors, 2019

Abstract

The world of molecular profiling has undergone revolutionary changes over the last few years as knowledge, technology, and even standard clinical practice have evolved. Broad molecular profiling is now nearly essential for all patients with metastatic solid tumors. New agents have been approved based on molecular testing instead of tumor site of origin. Molecular profiling methodologies have likewise changed such that tests that were performed on patients a few years ago are no longer complete and possibly inaccurate today. As with all rapid change, medical providers can quickly fall behind or struggle to find up‐to‐date sources to ensure he or she provides optimum care. In this review, the authors provide the current state of the art for molecular profiling/precision medicine, practice standards, and a view into the future ahead.

Wafik S. El‐Deiry MD, PhD, FACP

Associate Dean for Oncologic Sciences, Warren Alpert Medical School; Director, Joint Program in Cancer Biology, Brown University and the Lifespan Cancer Institute; Professor of Pathology & Laboratory Medicine and Professor of Medical Science, Brown University, Providence, RI

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Richard M. Goldberg MD

Professor of Medicine and Director, West Virginia University Cancer Institute, Morgantown, WV

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Heinz‐Josef Lenz MD, FAPC

Professor of Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA

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Anthony F. Shields MD, PhD

Professor of Oncology, Karmanos Cancer Institute, Detroit, MI

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Geoffrey T. Gibney MD

Associate Professor of Medicine, Co‐Leader of the Melanoma Disease Group, Lombardi Comprehensive Cancer Institute, MedStar Georgetown Cancer Institute, Washington, DC

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Antoinette R. Tan MD, MHSc

Co‐Director of Phase I Program, Department of Solid Tumor Oncology and Investigational Therapeutics, Levine Cancer Institute, Atrium Health, Charlotte, NC

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Jubilee Brown MD

Professor and Associate Director of Gynecologic Oncology, Levine Cancer Institute, Atrium Health, Charlotte, NC

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Burton Eisenberg MD

Professor of Clinical Surgery, University of Southern California, Los Angeles, CA

Executive Medical Director, Hoag Family Cancer Institute, Newport Beach, CA

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Elisabeth I. Heath MD, FACP

Professor of Oncology and Medicine, Karmanos Cancer Institute, Detroit, MI

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Surasak Phuphanich MD

Professor of Neurology, Director, Division of Neuro‐Oncology, Barrow Neurological Institute, Phoenix, AZ

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Edward Kim MD, FACP, FASCO

Chair, Solid Tumor Oncology and Investigational Therapeutics, Levine Cancer Institute, Atrium Health, Charlotte, NC

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Andrew J. Brenner MD, PhD

Associate Professor of Medicine, Mays Cancer Center at University of Texas Health San Antonio Cancer Center, San Antonio, TX

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John L. Marshall MD

Corresponding Author

E-mail address: marshalj@georgetown.edu

Professor of Medicine and Oncology, Director, Ruesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Institute, MedStar Georgetown Cancer Institute, Washington, DC

Corresponding author: John L. Marshall, MD, Ruesch Center for the Cure of GI Cancers, Lombardi Comprehensive Cancer Institute, MedStar Georgetown, 3800 Reservoir Road NW, Washington, DC 20007; E-mail address: marshalj@georgetown.edu

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First published: 22 May 2019
All authors are members of the Precision Oncology Alliance.
DISCLOSURES: Wafik El‐Deiry is the Scientific Founder and Shareholder in Oncoceutics, Inc as well as p53‐Therapeutics, Inc.; he is also cochair of the Caris Life Sciences Precision Oncology Alliance but receives no financial support from the company for research in connection with this role. Richard M. Goldberg reports travel support to consortium meetings from Caris Life Sciences and consulting on new product development for Taiho Pharmaceuticals, Novartis, and Merck. Heinz‐Josef Lenz reports grants, personal fees, and travel expenses from Bayer and personal fees from Merck Kg, Bristol‐Myers Squibb, and Genentech/Roche outside the submitted work. Anthony F. Shields reports research funding, personal fees, and travel expenses from Caris Life Sciences during the current study; research funding from Taiho Pharmaceuticals, Bayer, Boehringer Ingelheim, Plexicon, Eisai, H3 Biomedicine, Exelisis, Xencor, Lexicon, Daiichi Sankyo, Torque, Halozyme, Incyte, and LSK BioPharma outside the submitted work; personal fees and travel expenses from GE Health care outside the submitted work; and research funding, personal fees, and travel expenses from TransTarget and Inovio Pharmaceuticals outside the submitted work. Geoffrey T. Gibney reports personal fees from Novartis, Genentech, Merck, Bristol‐Myers Squibb, Array Biopharma, Jounce, and Newlink Genetics outside the submitted work. Antoinette R. Tan reports travel expenses from Caris Life Sciences during the current study and grants from Merck, Tesaro, Pfizer, and Genentech outside the submitted work. Jubilee Brown reports personal fees from Clovis, Tesaro, AstraZeneca, Biodesix, Caris Life Sciences, and Olympus outside the submitted work. Elisabeth I. Heath reports personal fees and honoraria from Dendreon during the conduct of the study; personal fees and travel expenses from Bayer, Sanofi, Seattle Genetics, Agensys Inc, and Sanofi outside the submitted work; grants and travel expenses from Caris Life Sciences outside the submitted work. Edward Kim reports grants from Roche, Boehringer Ingelheim, Pfizer, AstraZeneca, Merck, and Takeda outside the submitted work. John L. Marshall served as the interim Chief Medical Officer and is the ongoing Director of the Caris Life Sciences Precision Oncology Alliance; he reports personal fees from the company during the course of the study; and he reports grants and personal fees from Bayer, Celgene, Taiho Pharmaceuticals, and Merck outside the submitted work. All remaining authors report no conflicts of interest.

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