Late Effects of Childhood Leukemia Therapy

Fulbright, Joy M.; Raman, Sripriya; McClellan, Wendy; August, Keith J.

doi:10.1007/s11899-011-0094-x

Cited by 40 publications

(45 citation statements)

References 133 publications

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“…A hazai kezelési eredmények évek óta alig maradnak el a nyugat-európai országokban elértektől [34]. A magas túlélési esélyeknek megfelelően az utóbbi időben a figyelem középpontjába kerültek a daganatellenes terá-pia hosszú távú, késői szövődményei, amelyek erősen ronthatják a túlélők felnőttkori életminőségét [35,36].…”

Section: öSszefoglaló Közleményunclassified

Új és hagyományos irányok a gyermekkori akut lymphoblastos leukaemia biológiájában és ellátásában

et al. 2018

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Az utóbbi néhány évtized klinikai előrelépéseinek köszönhetően az akut lymphoblastos leukaemiás (ALL-) gyermekek nagy hányada ma az első vonalbeli kemoterápiás protokollok révén meggyógyul, és küzd a kortársak közé való visszatérés problémáival. Azonban a betegek jelentős részénél súlyos akut és késői terápiás mellékhatásokkal kell szá-molni. Emellett egyes betegcsoportok (például MLL-átrendeződéssel, hipodiploiditással, IKZF1-mutációval vagy korai prekurzor T-sejtes fenotípussal jellemezhető betegek) túlélése messze elmarad az átlagostól. Számukra nyújta-nak jobb klinikai kilátásokat az újabb betegellátási stratégiák: komplex géndiagnosztika, molekulárisan célzott daganatgátlás, immunonkológia és sejtterápia. Harminc feletti azon géneknek a száma, amelyek eltéréseit azonosították leukaemiás lymphoblastokban, és patobiológiai szerepük is valamennyire ismert. Ismerünk olyan betegcsoportot is (Philadelphia-like B-sejtes ALL), ahol a génexpressziós profilalkotás ad alapot a tirozin-kináz-inhibitorok használatá-nak. A leukaemiaasszociált immunfenotípus diagnóziskori áramlási citometriás meghatározásával és genetikai mód-szerekkel követhetővé vált a minimális residualis betegség. A blastfelszíni differenciációs klaszterek (elsősorban CD19, CD20 és CD22 a malignus B-sejteken) epitópjai monoklonális antitestekkel támadhatók. Fokozható a tumorellenes immunitás is, részben szintén a tumor sejtfelszíni markereinek (bispecifikus T-sejt-kapcsolóknál, kiméra antigénrecep-torú T-sejtes terápiánál), részben pedig a tumorspecifikus immunsejteknek (immunellenőrzőpont-gátlóknál) a kihasználása révén. A jelen közleményben áttekintést kívánunk adni a patogenetika új irányairól, a betegségkövetés modern módjairól és a célzott citotoxicitás innovatív lehetőségeiről biztató klinikai tanulmányok alapján. Orv Hetil. 2018; 159(20): 786-797. Keywords: akut lymphoblastos leukaemia, patogenezis, toxicitás, immunterápia, célzott molekuláris terápia New and traditional directions in the biology and management of childhood acute lymphoblastic leukemiaOwing to clinical trials and improvement over the past few decades, the majority of children with acute lymphoblastic leukemia (ALL) survive by first-line chemotherapy and combat with the problems of returning to community. However, many patients may have severe acute or late therapeutic side effects, and the survival rate in some groups (e.g., patients with MLL rearrangements, hypodiploidy, IKZF1 mutation or early precursor T cell phenotype) is far behind the average. Innovative strategies in medical attendance provide better clinical outcomes for them: complete gene diagnostics, molecularly targeted anticancer treatment, immuno-oncology and immune cell therapy. The number of genes with identified alterations in leukemic lymphoblasts is over thirty and their pathobiologic role is only partly clear. There are known patient groups where the use of specific drugs is based on gene expression profiling (e.g., tyrosine kinase inhibitors in Philadelphia-like B-cell ALL). The continuous assessment of min...

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Section: öSszefoglaló Közleményunclassified

Új és hagyományos irányok a gyermekkori akut lymphoblastos leukaemia biológiájában és ellátásában

et al. 2018

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“…While this finding is significantly elevated with cranial radiation, it is attenuated and associated with a later onset among those who have been treated with chemotherapy alone [67]. …”

Section: Neurotoxicitymentioning

confidence: 99%

Survivorship in Adolescents and Young Adults

Kishtagari¹,

Tavakkoli²,

Park³

2014

Acta Haematol

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In the USA, approximately 26,000 adolescents and young adults (AYAs) aged 15-29 years are diagnosed with cancer every year. The cure rate among this population exceeds 80%, resulting in a growing number of AYA cancer survivors. AYA cancer survivors suffer from a wide range of long-term treatment-related toxicities that adversely affect quality of life and increase the risk of premature death. Therefore, it is important to recognize the unique medical needs of the AYA cancer survivors and develop a cost-effective and systemic approach to screen and prevent cancer treatment-related sequelae and the adverse health outcomes.

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Section: Introductionmentioning

confidence: 99%

“…It has been shown that there are short and long term adverse effects of chemotherapy. Both adult and pediatric cancer survivors face significant health burdens including but not limited to impaired end-organ function, risk of secondary cancers and shortened life expectancies [1,2].Development of personalized medicine strategy is becoming more popular. It focuses on identifying drugs that can target a molecular pathway or more specifically a protein involved in an uncontrolled or disrupted signaling pathway leading to the progression of particular cancer.…”

mentioning

confidence: 99%

High Throughput Screening of Small Molecule Library: Procedure, Challenges and Future

Shukla¹

2016

JCPCR

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High-throughput screening (HTS) of small molecules is used to identify and characterize chemical compounds based on their response on particular assays. The screened compounds can be further used as tools to study complex molecular pathways involved in progression of cancers and potential candidates can be further developed as drugs. Testing of vast number of compounds and fast readout technologies for assays in a timely manner has made this procedure a popular drug-discovery process, which is widely used in the pharmaceutical industry. However, the procedure of screening is a multi-step process and is prone to give false positive and false negative results. Assurance of quality and good analysis of results play critical role in finding a true product. Technological hardware like robotic plate handling is critical for the procedure. Reagents like antibodies and recombinant proteins can also make the whole procedure very expensive. Increased number of available compounds and molecular targets has raised the requirements for even faster procedures, more sensitive assays to run and even smaller sample size assays for screening. Development of new methods like Droplet-based cell encapsulation technology has given hope for a better future of HTS. Keywords: High-throughput screening (HTS); Small molecules; Target identification; Assay design IntroductionCancer kills around 7.6 million people worldwide every year and about a half million people in the US annually. Early detection and more effective chemotherapy have improved cure rate among patients. However, patients diagnosed with advanced stage cancers still have very few options for treatment. It has been shown that there are short and long term adverse effects of chemotherapy. Both adult and pediatric cancer survivors face significant health burdens including but not limited to impaired end-organ function, risk of secondary cancers and shortened life expectancies [1,2].Development of personalized medicine strategy is becoming more popular. It focuses on identifying drugs that can target a molecular pathway or more specifically a protein involved in an uncontrolled or disrupted signaling pathway leading to the progression of particular cancer. Genetics studies are confirming addictions and weaknesses of cancer cells on such pathways and specific molecules. With this approach, normal tissues are spared from getting targeted by toxic chemotherapies.Drug discovery programs start to find a cure for a disease, which does not have suitable treatment available. Data generated by primary research suggest involvement of specific proteins in the progression of diseases and can be used as target for drug development [3]. An assay is then developed that can be used to screen small molecule chemical libraries The whole process of HTS can be divided into steps of target identification, assay design, primary and secondary screens, data analysis and identification of hits (Figure 1). The role of HTS is not only limited to identifying new compounds but is also useful in ass...

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Late Effects of Childhood Leukemia Therapy

Cited by 40 publications

References 133 publications

Új és hagyományos irányok a gyermekkori akut lymphoblastos leukaemia biológiájában és ellátásában

Új és hagyományos irányok a gyermekkori akut lymphoblastos leukaemia biológiájában és ellátásában

Survivorship in Adolescents and Young Adults

High Throughput Screening of Small Molecule Library: Procedure, Challenges and Future

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