INHOUDSOPGAVE
1. CELDELING ALS MOTOR VAN ONTWIKKELING, GROEI EN WEEFSELHOMEOSTASE ........ 12
2. NEOPLASTISCHE GROEI ............................................................................................. 12
3. INVASIEF EN METASTATISCH GEDRAG ........................................................................ 13
4. SELECTIE VAN TUMORCELLEN .................................................................................... 14
DE "HALLMARKS OF CANCER" .............................................................................................. 14
1) ZELFVOORZIENEND IN GROEIFACTOREN .................................................................................... 15
2) ONGEVOELIG VOOR GROEIREMMENDE SIGNALEN ........................................................................ 15
3) VERMIJDEN VAN CELDOOD (APOPTOSE) .................................................................................... 15
4) ONBEPERKTE CELDELING (IMMORTALISATIE) ............................................................................... 16
5) INDUCTIE VAN ANGIOGENESE ................................................................................................. 16
6) ACTIVATIE VAN INVASIE EN METASTASERING ............................................................................... 17
AANVULLENDE HALLMARKS (2011: +4 KENMERKEN)................................................................... 17
7) GENOMISCHE INSTABILITEIT EN MUTATIES .................................................................................. 17
8) TUMOR-BEVORDERENDE INFLAMMATIE ..................................................................................... 17
9) HERPROGRAMMEREN VAN ENERGIEMETABOLISME ....................................................................... 18
10) ONTWIJKEN VAN HET IMMUUNSYSTEEM ................................................................................... 18
AANVULLENDE HALLMARKS (2022: +4 KENMERKEN)................................................................... 18
11) FENOTYPISCHE PLASTICITEIT ONTSLUITEN ................................................................................ 18
12) EPIGENETISCHE HERPROGRAMMERING ................................................................................... 18
13) BELANG VAN HET MICROBIOOM ............................................................................................. 19
14) SENESCENTE CELLEN.......................................................................................................... 19
BELANGRIJK: TUMOR MICRO-OMGEVING ....................................................................... 19
BELANGRIJK: ONTWIKKELEN VAN DOELGERICHTE ANTI-KANKERTHERAPIEËN ................ 19
5. HOE MANIFESTEERT KANKER ZICH IN EEN PATIËNT? ................................................... 19
1
,6. TUMORCLASSIFICATIE ............................................................................................... 20
HERHALING: HALLMARKS OF CANCER (EERSTE 10) ......................................................... 22
RECENT TOEGEVOEGDE 4 KENMERKEN (14 HALLMARKS TOTAAL):................................................... 22
2 GROTE CATEGORIEËN VAN GENEN .............................................................................. 22
1. ONCOGENEN ................................................................................................................ 22
MECHANISMEN VAN VIRALE ONCOGENESE .................................................................................... 23
GENETISCHE MECHANISMEN DIE LEIDEN TOT CONSTITUTIEVE ACTIVATIE VAN ONCOGENEN BIJ DE MENS ....... 24
2. TUMORSUPPRESSORGENEN (TSG) ..................................................................................... 27
"TWO-HIT"-HYPOTHESE VAN KNUDSON ........................................................................................ 27
TUMORSUPPRESSORGENEN ....................................................................................................... 30
KANKER ALS ZIEKTE VAN DE CELCYCLUS ....................................................................... 30
1. APOPTOSE IN CARCINOGENESE EN KANKERBEHANDELING ........................................ 31
APOPTOSE = GEPROGRAMMEERDE CELDOOD ............................................................................ 31
VERSTORING APOPTOSE = CENTRALE STAP IN TUMORALE TRANSFORMATIE! ....................................... 31
A) APOPTOSE VS. NECROSE ....................................................................................................... 31
B) MORFOLOGISCHE KENMERKEN VAN APOPTOSE ........................................................................... 32
C) APOPTOSE VERLOOPT IN 3 FASEN ............................................................................................ 32
D) DE EXECUTIEFASE VAN APOPTOSE ............................................................................................ 33
E) DE INTRINSIEKE OF MITOCHONDRIALE PATHWAY .......................................................................... 33
F) DE EXTRINSIEKE OF 'DEATH RECEPTOR' PATHWAY ......................................................................... 35
G) DE APOPTOSE-CASCADE ALS DOELWIT VOOR ANTIKANKERTHERAPIE ................................................ 35
2. P53: BEWAKER VAN HET GENOOM ....................................................................................... 36
A) HISTORIEK VAN P53 .............................................................................................................. 36
B) STRUCTUUR VAN WILD TYPE EN GEMUTEERD P53 ......................................................................... 36
C) REGELING VAN P53-CONCENTRATIE EN -ACTIVITEIT IN BASALE OMSTANDIGHEDEN .............................. 37
D) REGELING VAN P53-CONCENTRATIE EN -ACTIVITEIT IN ABNORMALE OMSTANDIGHEDEN ....................... 37
2
,E) CELLULAIRE EFFECTEN VAN VERHOOGDE P53-ACTIVITEIT .............................................................. 37
F) P53 ALS AANGRIJPINGSPUNT VOOR MOLECULAIRE ANTIKANKERTHERAPIE .......................................... 39
1. INTRODUCTIE ............................................................................................................ 40
RADIOTHERAPIE WERKT! ...................................................................................................... 40
IRIDIUM NETWERK ANTWERPEN ............................................................................................ 40
MULTIDISCIPLINAIR CONSULT (MOC) ..................................................................................... 40
DOEL VAN DE BEHANDELING ................................................................................................. 40
2. RADIOTHERAPIE IN DE PRAKTIJK................................................................................. 40
WAT IS RADIOTHERAPIE? ..................................................................................................... 40
ATOOMSTRUCTUUR & IONISATIE ............................................................................................ 41
SOORTEN STRALING ........................................................................................................... 41
EENHEID VAN STRALING ...................................................................................................... 41
TUMOR VERDUBBELINGSTIJD................................................................................................. 41
TUMORBIOLOGIE ............................................................................................................... 42
HOE WERKT RADIOTHERAPIE? ............................................................................................... 42
EFFECT VAN STRALING OP WEEFSELS ...................................................................................... 42
FRACTIONERING ................................................................................................................ 43
DOEL VAN RADIOTHERAPIE ................................................................................................... 43
THERAPEUTISCHE BREEDTE .................................................................................................. 43
RADIORESISTENTIE ............................................................................................................ 43
POGINGEN TOT VERBETERING VAN EFFECTIVITEIT ....................................................................... 43
COMBINATIEBEHANDELINGEN .............................................................................................. 44
WIE KOMT IN AANMERKING VOOR RADIOTHERAPIE? .................................................................... 44
HOE LANG BESTAAT RADIOTHERAPIE? ..................................................................................... 44
BRACHYTHERAPIE .............................................................................................................. 44
WAT HEB JE NODIG VOOR MODERNE RADIOTHERAPIE................................................................... 45
3
, MACHINERIE........................................................................................................................... 45
MENSEN ................................................................................................................................ 45
CT/MRI DOSIMETRIE & BEELDVORMING .................................................................................. 45
TREATMENT PLANNING SYSTEM............................................................................................. 45
BEELDGESTUURDE PLANNING ............................................................................................... 46
LINEAIRE VERSNELLER: TECHNIEK .......................................................................................... 46
3. BIJWERKINGEN RADIOTHERAPIE ................................................................................ 46
INDELING: ACUUT VS. LAAT................................................................................................... 46
ACUTE BIJWERKINGEN ........................................................................................................ 46
LATE BIJWERKINGEN ........................................................................................................... 47
4. MODERNE RADIOTHERAPIE ........................................................................................ 47
ONTWIKKELING IN TECHNIEK ................................................................................................ 47
WAAROM NIEUWE TECHNIEKEN NODIG? .................................................................................. 47
WAARDOOR WERD HET MOGELIJK? ........................................................................................ 47
WAT IS BELANGRIJK BIJ DE NIEUWE TECHNIEKEN? ....................................................................... 47
KLASSIEKE RADIOTHERAPIE .................................................................................................. 47
IMRT: INTENSITEITSGEMODULEERDE RADIOTHERAPIE ................................................................. 48
4D: ADEMHALINGSGECONTROLEERDE RT ................................................................................ 48
IMAGE GUIDED RADIOTHERAPIE (IGRT) ................................................................................... 48
5. NIEUWE ONTWIKKELINGEN ........................................................................................ 48
RECENTE ONTWIKKELINGEN (OVERZICHT) ................................................................................ 48
GOUDMARKERS (VISICOILS®) ................................................................................................ 48
STEREOTACTISCHE RADIOCHIRURGIE EN RADIOTHERAPIE ............................................................ 48
SBRT WERVELMETASTASEN ................................................................................................. 49
MRI-GELEIDE RADIOTHERAPIE .............................................................................................. 49
PROTON/HADRON THERAPIE ................................................................................................ 49
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1. CELDELING ALS MOTOR VAN ONTWIKKELING, GROEI EN WEEFSELHOMEOSTASE ........ 12
2. NEOPLASTISCHE GROEI ............................................................................................. 12
3. INVASIEF EN METASTATISCH GEDRAG ........................................................................ 13
4. SELECTIE VAN TUMORCELLEN .................................................................................... 14
DE "HALLMARKS OF CANCER" .............................................................................................. 14
1) ZELFVOORZIENEND IN GROEIFACTOREN .................................................................................... 15
2) ONGEVOELIG VOOR GROEIREMMENDE SIGNALEN ........................................................................ 15
3) VERMIJDEN VAN CELDOOD (APOPTOSE) .................................................................................... 15
4) ONBEPERKTE CELDELING (IMMORTALISATIE) ............................................................................... 16
5) INDUCTIE VAN ANGIOGENESE ................................................................................................. 16
6) ACTIVATIE VAN INVASIE EN METASTASERING ............................................................................... 17
AANVULLENDE HALLMARKS (2011: +4 KENMERKEN)................................................................... 17
7) GENOMISCHE INSTABILITEIT EN MUTATIES .................................................................................. 17
8) TUMOR-BEVORDERENDE INFLAMMATIE ..................................................................................... 17
9) HERPROGRAMMEREN VAN ENERGIEMETABOLISME ....................................................................... 18
10) ONTWIJKEN VAN HET IMMUUNSYSTEEM ................................................................................... 18
AANVULLENDE HALLMARKS (2022: +4 KENMERKEN)................................................................... 18
11) FENOTYPISCHE PLASTICITEIT ONTSLUITEN ................................................................................ 18
12) EPIGENETISCHE HERPROGRAMMERING ................................................................................... 18
13) BELANG VAN HET MICROBIOOM ............................................................................................. 19
14) SENESCENTE CELLEN.......................................................................................................... 19
BELANGRIJK: TUMOR MICRO-OMGEVING ....................................................................... 19
BELANGRIJK: ONTWIKKELEN VAN DOELGERICHTE ANTI-KANKERTHERAPIEËN ................ 19
5. HOE MANIFESTEERT KANKER ZICH IN EEN PATIËNT? ................................................... 19
1
,6. TUMORCLASSIFICATIE ............................................................................................... 20
HERHALING: HALLMARKS OF CANCER (EERSTE 10) ......................................................... 22
RECENT TOEGEVOEGDE 4 KENMERKEN (14 HALLMARKS TOTAAL):................................................... 22
2 GROTE CATEGORIEËN VAN GENEN .............................................................................. 22
1. ONCOGENEN ................................................................................................................ 22
MECHANISMEN VAN VIRALE ONCOGENESE .................................................................................... 23
GENETISCHE MECHANISMEN DIE LEIDEN TOT CONSTITUTIEVE ACTIVATIE VAN ONCOGENEN BIJ DE MENS ....... 24
2. TUMORSUPPRESSORGENEN (TSG) ..................................................................................... 27
"TWO-HIT"-HYPOTHESE VAN KNUDSON ........................................................................................ 27
TUMORSUPPRESSORGENEN ....................................................................................................... 30
KANKER ALS ZIEKTE VAN DE CELCYCLUS ....................................................................... 30
1. APOPTOSE IN CARCINOGENESE EN KANKERBEHANDELING ........................................ 31
APOPTOSE = GEPROGRAMMEERDE CELDOOD ............................................................................ 31
VERSTORING APOPTOSE = CENTRALE STAP IN TUMORALE TRANSFORMATIE! ....................................... 31
A) APOPTOSE VS. NECROSE ....................................................................................................... 31
B) MORFOLOGISCHE KENMERKEN VAN APOPTOSE ........................................................................... 32
C) APOPTOSE VERLOOPT IN 3 FASEN ............................................................................................ 32
D) DE EXECUTIEFASE VAN APOPTOSE ............................................................................................ 33
E) DE INTRINSIEKE OF MITOCHONDRIALE PATHWAY .......................................................................... 33
F) DE EXTRINSIEKE OF 'DEATH RECEPTOR' PATHWAY ......................................................................... 35
G) DE APOPTOSE-CASCADE ALS DOELWIT VOOR ANTIKANKERTHERAPIE ................................................ 35
2. P53: BEWAKER VAN HET GENOOM ....................................................................................... 36
A) HISTORIEK VAN P53 .............................................................................................................. 36
B) STRUCTUUR VAN WILD TYPE EN GEMUTEERD P53 ......................................................................... 36
C) REGELING VAN P53-CONCENTRATIE EN -ACTIVITEIT IN BASALE OMSTANDIGHEDEN .............................. 37
D) REGELING VAN P53-CONCENTRATIE EN -ACTIVITEIT IN ABNORMALE OMSTANDIGHEDEN ....................... 37
2
,E) CELLULAIRE EFFECTEN VAN VERHOOGDE P53-ACTIVITEIT .............................................................. 37
F) P53 ALS AANGRIJPINGSPUNT VOOR MOLECULAIRE ANTIKANKERTHERAPIE .......................................... 39
1. INTRODUCTIE ............................................................................................................ 40
RADIOTHERAPIE WERKT! ...................................................................................................... 40
IRIDIUM NETWERK ANTWERPEN ............................................................................................ 40
MULTIDISCIPLINAIR CONSULT (MOC) ..................................................................................... 40
DOEL VAN DE BEHANDELING ................................................................................................. 40
2. RADIOTHERAPIE IN DE PRAKTIJK................................................................................. 40
WAT IS RADIOTHERAPIE? ..................................................................................................... 40
ATOOMSTRUCTUUR & IONISATIE ............................................................................................ 41
SOORTEN STRALING ........................................................................................................... 41
EENHEID VAN STRALING ...................................................................................................... 41
TUMOR VERDUBBELINGSTIJD................................................................................................. 41
TUMORBIOLOGIE ............................................................................................................... 42
HOE WERKT RADIOTHERAPIE? ............................................................................................... 42
EFFECT VAN STRALING OP WEEFSELS ...................................................................................... 42
FRACTIONERING ................................................................................................................ 43
DOEL VAN RADIOTHERAPIE ................................................................................................... 43
THERAPEUTISCHE BREEDTE .................................................................................................. 43
RADIORESISTENTIE ............................................................................................................ 43
POGINGEN TOT VERBETERING VAN EFFECTIVITEIT ....................................................................... 43
COMBINATIEBEHANDELINGEN .............................................................................................. 44
WIE KOMT IN AANMERKING VOOR RADIOTHERAPIE? .................................................................... 44
HOE LANG BESTAAT RADIOTHERAPIE? ..................................................................................... 44
BRACHYTHERAPIE .............................................................................................................. 44
WAT HEB JE NODIG VOOR MODERNE RADIOTHERAPIE................................................................... 45
3
, MACHINERIE........................................................................................................................... 45
MENSEN ................................................................................................................................ 45
CT/MRI DOSIMETRIE & BEELDVORMING .................................................................................. 45
TREATMENT PLANNING SYSTEM............................................................................................. 45
BEELDGESTUURDE PLANNING ............................................................................................... 46
LINEAIRE VERSNELLER: TECHNIEK .......................................................................................... 46
3. BIJWERKINGEN RADIOTHERAPIE ................................................................................ 46
INDELING: ACUUT VS. LAAT................................................................................................... 46
ACUTE BIJWERKINGEN ........................................................................................................ 46
LATE BIJWERKINGEN ........................................................................................................... 47
4. MODERNE RADIOTHERAPIE ........................................................................................ 47
ONTWIKKELING IN TECHNIEK ................................................................................................ 47
WAAROM NIEUWE TECHNIEKEN NODIG? .................................................................................. 47
WAARDOOR WERD HET MOGELIJK? ........................................................................................ 47
WAT IS BELANGRIJK BIJ DE NIEUWE TECHNIEKEN? ....................................................................... 47
KLASSIEKE RADIOTHERAPIE .................................................................................................. 47
IMRT: INTENSITEITSGEMODULEERDE RADIOTHERAPIE ................................................................. 48
4D: ADEMHALINGSGECONTROLEERDE RT ................................................................................ 48
IMAGE GUIDED RADIOTHERAPIE (IGRT) ................................................................................... 48
5. NIEUWE ONTWIKKELINGEN ........................................................................................ 48
RECENTE ONTWIKKELINGEN (OVERZICHT) ................................................................................ 48
GOUDMARKERS (VISICOILS®) ................................................................................................ 48
STEREOTACTISCHE RADIOCHIRURGIE EN RADIOTHERAPIE ............................................................ 48
SBRT WERVELMETASTASEN ................................................................................................. 49
MRI-GELEIDE RADIOTHERAPIE .............................................................................................. 49
PROTON/HADRON THERAPIE ................................................................................................ 49
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