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6 december 2016: Bron: Seminars in Cancer biology December 2015, Pages S276–S304 A broad-spectrum integrative design for cancer prevention and therapy
Bepaalde niet-toxische middelen - voedingstoffen / kruiden (red: Fytotherapie) waaronder ook TCM - Traditionele Chinese kruiden zouden een grote rol kunnen spelen in het verbeteren van de therapeutische effectiviteit van gerichte medicijnen en in het voorkomen van een recidief en in het verminderen van de bijwerkingen binnen het veld van targeted therapy en personalised medicine. Maar liefst 67 procent van een integrale aanpak zou het positieve effect zijn van de aanvullende niet-toxische middelen en voedingsstoffen op de klinische resultaten van de voorgestelde behandelingen plus aanvullende middelen. Neem dit rapport maar eens mee naar uw oncoloog als zij/hij zich negateif uitlaat over aanvullende niet-toxische middelen.
Dit stelt een groep van 180 top wetenschappers in een rapport dat ze hebben opgesteld op basis van de literatuur binnen evidence based medicine. Zij stellen ook dat met deze integrale aanpak van reguliere en complementaire aanpak de kosten van personalised medicine drastisch omlaag kunnen en daarmee ook voor iedereen beschikbaar en betaalbaar worden. Elsevier heeft dit rapport in Science Direct gepubliceerd onder de titel A broad-spectrum integrative design for cancer prevention and therapy. Tekst gaat verder onder foto
Het is m.i. een geweldig rapport. Zeer goed en duidelijk beschreven met een geweldige referentielijst (zie onderaan dit artikel), ook van de niet-toxische middelen en voedingsstoffen. Die zover ik heb gecontroleerd ook allemaal voorkomen in de literatuurlijsten van arts-bioloog drs. Engelbert Valstar. En nu dus bevestigd door een International Task Force van maar liefst 180 top wetenschappers en oncologen.
Zo wordt dit rapport ingeleid (vrij vertaald):
Gerichte therapieën en de daaruit voortvloeiende invoering van "gepersonaliseerde behandelingen / medicijnen" hebben opmerkelijke successen bij sommige vormen van kanker gerealiseerd; echter er blijven nog aanzienlijke problemen zich voordoen met deze aanpak. Veel gerichte behandelingen geven ernstige bijwerkingen, de kosten ervan zijn zeer hoog en de meeste patiënten ervaren een terugval / recidief na een paar ziektevrije maanden. Recidieven ontstaan door de genetische heterogeniteit in tumoren, die ook therapie resistente cellen bevatten en die wisselende ontsnappingspaden / trajecten (pathways) hebben aangenomen, (dat wil zeggen, paden die niet zijn gebaseerd op dezelfde mechanismen als die waarop de behandelingen / medicijnen zijn gericht).
Om deze beperkingen aan te pakken, werd een internationale task force van 180 wetenschappers samengesteld om een concept te maken van een therapeutische aanpak met een breed spectrum van een lage toxiciteit en tegelijk een veelomvattende aanpak van bekende paden (pathways) en bepaalde mechanismes.
Met behulp van bepaalde bekende biomarkers van kanker en de tumor micro-omgeving om zo rekening te houden met de verschillende aspecten van een relevante kanker biologie, hebben interdisciplinaire teams elke biomarker beoordeeld en een breed scala aan doelstellingen met een hoge prioriteit (74 in totaal) genomineerd die zouden kunnen worden aangepast om de klinische resultaten voor patiënten te verbeteren. Voor deze doelstellingen werden hiermee samenhangende lage toxiciteit therapeutische benaderingen voorgesteld, waarvan vele vallend binnen de zogeheten fytotherapie (Red: niet-toxische middelen zoals kruiden en bepaalde voedingstoffen).
Tekst gaat verder onder foto / grafiek
Resultaten:
Voorgestelde maatregelen voor elk apart benoemd doel en alle voorgestelde benaderingen werden verder beoordeeld op bekende effecten op bepaalde biomarkers en de tumor micro-omgeving.
- Potentiële kankerbevorderende effecten werden gevonden bij 3,9% gerelateerd aan het verband tussen gerichtheid (doel) en biomarkers.
- Een gemengde bewijs van complementaire en anders verbanden weerden gevonden bij 7,1%.
- Ongeveer 67% bleek gerelateerd aan potentieel positieve aanvullende effecten, en de rest had geen bekende relatie.
- Onder de benaderingen had 1,1% een negatief effect, 2,8% een gemengd effect en 62,1% had aanvullende positieve effecten.
Conclusie van de onderzoekers:
Deze resultaten suggereren dat een breed spectrum benadering uit veiligheidsoogpunt mogelijk en toepasbaar moet zijn. Deze nieuwe benadering kan relatief goedkoop zijn en het moet ons helpen stadia en vormen van kanker aan te pakken waarvoor een conventionele behandeling ontbreekt. En het kan de kans op recidieven verminderen. Een voorgestelde agenda voor toekomstig onderzoek wordt aangeboden.
Het volledige studierapport: Designing a broad-spectrum integrative approach for cancer prevention and treatment is gratis in te zien met een geweldige referentielijst onderaan dit artikel.
Hier het abstract / inleiding van dit studierapport
These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks.
Volume 35, Supplement, December 2015, Pages S276–S304
A broad-spectrum integrative design for cancer prevention and therapy
Designing a broad-spectrum integrative approach for cancer prevention and treatment
- Keith I. Blocka, , ,
- Charlotte Gyllenhaala,
- Leroy Loweb, er, , ,
- Amedeo Amedeic,
- A.R.M. Ruhul Amind,
- Amr Amine,
- Katia Aquilanof,
- Jack Arbiserd, ep, eq,
- Alexandra Arreolag,
- Alla Arzumanyanh,
- S. Salman Ashrafi,
- Asfar S. Azmij,
- Fabian Benenciak,
- Dipita Bhaktal,
- Alan Bilslandm,
- Anupam Bishayeen,
- Stacy W. Blaino,
- Penny B. Blocka,
- Chandra S. Boosanip,
- Thomas E. Careyq,
- Amancio Carneror,
- Marianeve Carotenutos, t,
- Stephanie C. Caseyu,
- Mrinmay Chakrabartiv,
- Rupesh Chaturvediw,
- Georgia Zhuo Chend,
Open Access
Abstract
Targeted therapies and the consequent adoption of “personalized” oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity “broad-spectrum” therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment.
Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships.
These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered.
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Copyright © 2015 The Authors. Published by Elsevier Ltd.
complementair, voedingsupplementen, fruit en groenten, antioxidanten, voeding, literatuurlijst, niet-toxische middelen en behandelingen, preventie, voorkomen van recidief, personalised medicine, targeted therapy, gerichte medicijnen, TCM, Chinese kruiden, bijwerkingen, klinische effectiviteit, International task force
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- De biologische processen waarom en hoe kankercellen uitzaaien wordt beter begrepen, tumorcellen vroeger ontdekt en lijkt ook steeds beter te behandelen
- De huidige staat van moleculair testen in het behandelen van kankerpatienten met solide tumoren. Een uitstekend overzichtsartikel met de nieuwste ontwikkelingen over RNA, DNA en eiwitten anno 2019
- Diagnosetest PERCEPTION via AI - Kunstmatige Intelligentie ontwikkeld en met hulp van single-cell RNA-sequencing voorspelt nauwkeurig of een specifiek medicijn van de kankerpatient zal aanslaan of resistent zal zijn.
- DRUP studie geeft bij 37 procent van de patienten alsnog een therapeutisch effect met 6 procent CR en 14 procent PR en 17 procent stabiele ziekte
- EMA: Veel nieuwe kankermedicijnen in de EU hebben geen bewezen toegevoegde waarde blijkt uit Nederlandse studie naar goedgekeurde kankermedicijnen door het Europees Geneesmiddelenbureau (EMA).
- ESMO - European Society for Medical Oncology heeft een gids uitgegeven voor patienten over hoe personalised medicine werkt en stand van zaken
- FDA ondersteunt onderzoek naar personalised medicine op basis van mutaties ongeacht in welk lichaamsdeel de kanker zich het eerst openbaart.
- Genetisch onderzoek via Germline testen (kiembaan testen) werd in periode 2013 tot 2019 in Georgie en Californie bij slechts 7 procent gedaan onder 1 369 602 patienten met twee jaar kanker.
- Geneesmiddel (ARS1620) verandert kankergen (KRAS mutatie) dat kwaadaardige tumoren beschermt tegen immuunsysteem in een doelwit voor immuunsysteem en helpt immuuntherapie kankercellen te elimineren
- Gentherapie zoals Chrispr-cas en base-editors zijn zeer succesvol bij erfelijke ziekten waaronder ook vormen van kanker zoals sikkelcelziekte
- Gerichte behandelingen met Aurora kinaseremmers geven soms uitstekende resultaten bij veel vormen van kanker. Een reviewstudie
- Immuuntherapie met HER2-gerichte CT-0508 (CAR-Macrofaag therapie) geeft bij solide tumoren van verschillende vormen van kanker met HER2 positieve expressie hoopvolle resultaten
- Immuuntherapie met pembrolizumab bij patiënten met verschillende vormen van uitgezaaide kanker met hoge microsatellietinstabiliteit (MSI-H) en DNA-mismatch-reparatie-deficiënte (dMMR) geeft uitstekende en duurzame resultaten op overall overleving
- Immuuntherapie met nivolumab zorgt voor duurzame en sterk verbeterde overall overleving bij verschillende vormen van kanker, melanomen, longkanker en nierkanker copy 1
- Internationale groep van 180 wetenschappers stelt rapport op hoe en met welke niet-toxische middelen - voedingsstoffen de effectiviteit te verbeteren, recidieven te voorkomen en de bijwerkingen te verminderen van personalised medicine
- Irina Kareva gebruikt wiskundige modellen die de dynamiek van kanker beschrijven, met het doel nieuwe geneesmiddelen te ontwikkelen die gericht zijn op tumoren.
- Kanker-actueel kan en wil helpen - begeleiden bij aanvragen van een volledig biomoleculair receptorenonderzoek en genenonderzoek
- Kankermedicijnen geven in de klinische praktijk veel minder effect dan uit de studies van farmaceutische bedrijven is aangetoond. Maar zijn wel ontzettend duur.
- Kankerremmende eiwitten kunnen bij mutatie die gen uitschakelt veranderen van kankerremmend in stimulerend, ontdekten Nederlandse onderzoekers
- Larotrectinib geeft bijzonder goede resultaten (76 procent respons met 12 procent complete remissies) bij alle vormen van solide tumoren met een positieve TRK Fusion mutatie
- Larotrectinib: Met de goedkeuring van Larotrectinib op basis van 1 specifieke afwijking en niet op basis van primaire tumor zorgt de FDA voor een doorbraak in het behandelen van kanker
- Lenvatinib Plus Pembrolizumab bij patiënten met inoperabele gevorderde nierkanker, buikvlieskanker, melanomen en andere gevorderde kanker met solide tumoren geeft uitstekende resultaten met meer dan de helft remissies van 50 procent of meer copy 1
- Medicijnen voorschrijven op basis van DNA profiel van de patient voorkomt 30 procent minder bijwerkingen blijkt uit internationale studie onder leiding van LUMC Leiden
- MSC-1 een medicijn dat de groei van de kankerstamcellen afremt door LIF blokkade en immuunsysteem activeert laat spectaculair goede resultaten zien in fase I studie.
- Mytomorrows breidt aanbod aan experimentele medicijnen voor kankerpatienten uit met 11 nieuwe nog niet geregistreerde medicijnen en stelt deze beschikbaar voor uitbehandelde kankerpatienten
- Nederland betaalt veel meer voor kankermedicijnen, soms tot 50 procent of meer, dan andere landen blijkt uit vergelijkend onderzoek tussen 18 landen copy 1
- NCI-MATCH-studie toont aan dat een biomoleculaire analyse - DNA en receptorenonderzoek - belangrijk is in hoe een kankerpatient te behandelen.
- Nieuw medicijn - PD-0332991 - stopt groei hersentumoren Glioblastoom in dierproeven. Zodra gestopt werd met dit medicijn gingen de tumoren weer groeien. Fase I studie bij 33 patienten met nierkanker en lymfklierkanker bevestigt veiligheid van dit middel
- Nieuwe, dure kankermedicijnen zijn voortaan sneller beschikbaar door het Drug Access Protocol (DAP) dat is ontwikkeld door oncologen, verzekeraars en Zorginstituut Nederland
- Overzicht van alle wereldwijd geregistreerde medicijnen binnen immuuntherapie en lopende studies met immuuntherapie copy 1
- Overzicht van studies met medicijnen en behandelingen om tumoren met KRAS mutaties aan te pakken. Vooral combinatiebehandelingen zijn veelbelovend.
- PI3K/AKT/mTOR pathway speelt cruciale rol in apoptose proces, DNA herstel, metabolisme in de cel en angiogenese.
- Pembrolizumab - Keytruda geeft bij solide tumoren van verschillende oorsprong 21 procent complete remissies en 53 procent gedeeltelijke remissies.
- Personalised medicine door receptorenonderzoek geeft veel betere resultaten in fase 1 studies dan experimenteel onderzoek zonder receptorenonderzoek
- Prof. Bernards over de doorbraak bij darmkanker met Kras mutatie en bij melanomen met BRAF mutatie in DWDD van donderdag 27 maart 2014
- POLE mutatie: veel kankerpatienten met erfelijke vormen van kanker hebben naast een P1-ligand een POLE mutatie en reageren goed op immuuntherapie met anti-PD medicijnen - checkpointremmers als pembrolizumab en nivolumab
- Radiotherapeutisch stimulerend middel NBTXR3 geeft in combinatie met anti-PD-1 medicijnen alsnog uitstekende resultaten bij patiënten die ziekteprogressie lieten zien ongeacht eerdere behandeling met anti-PD-1 medicijnen
- Rozlytrek (entrectinib), een tyrosine kinase remmer, goedgekeurd door FDA als medicijn voor solide tumoren met NTRK (neurotrophic tyrosine receptor kinase) gene fusion. Dit is 3e goedgekeurde medicijn op basis van mutatie.
- Tweede primaire vorm van kanker bij een kankerpatient wordt steeds vaker bekend bij de diagnose (2 tot 17 procent) door betere diagnose technieken en verfijnder biomoleculair onderzoek
- Tumorindeling mede aan de hand van biomarkers - biomoleculaire profielen is nodig en zal behandelingen sterk veranderen voor veel kankerpatiënten. Van 10 procent nu tot 50 procent straks. Aldus grote studie van het TOGA
- Vaccin tegen KRAS positief gemuteerde vormen van kanker - darmkankers en longkanker o.a. - wordt gecombineerd met trametinib een anti-PD medicijn in fase I studie na hoopvolle resultaten.
- Voorbeeldrapporten van receptoren en DNA testen - biomoleculaire profielen uitgevoerd door Caris Lifesciences - van alvleesklierkanker, hersentumoren, melanomen en longkanker
- Vroege diagnose van kanker is de toekomst en is vaak al mogelijk: zie TED talk
- Ziekte van Parkinson: prasinezumab, een monoklonaal antilichaam dat alfa-synucleïne bindt, vertraagt sterk de progressie van de ziekte van Parkinson in vergelijking met patienten die beste zorg kregen
- Algemeen: overzicht van artikelen waarin personal medicine een rol speelt.
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