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RECEPTOR DE FOLATO Y CANCER XIV Congreso Nacional Salamanca Octubre de 2013
Simposio Científico Especial MSD 13-14,15h
Andres Poveda, MD Fundación Instituto Valenciano de Oncología
Origen del folato en humanos
pteroylmonoglutamic acid
FOLATO= vitamina B9
ÁCIDO FÓLICO
British Journal of Nutrition(2001), 85, Suppl. 2,
S115±S124
60% legumbres + cereales
ALIMENTACIÓN= FUENTE EXTERNA
ENFERMEDADES ASOCIADAS DÉFICIT FOLATO
1) Anemia megaloblástica
2) Malformaciones recién nacido: maduración tubo neural
3) Homocisteinemia (¿?)
1) Acumulación de homocisteina
2) Efectos: factor riesgo cardiovascular: infartos,….
British Journal of Nutrition(2001), 85, Suppl. 2,
S115±S124
Folato: Key Points
Se come
Básico en la Síntesis de DNA
Parece pueda tener una relación con el
tratamiento del cáncer
Historia de la inhibición de folatos
en cáncer
Drogas clásicas antifolato:
Metrotexate
Indicaciones: LLA, Osteosarcoma, Coriocarcinoma
(ETG), CM,Ca Vejiga,
Inmunosupresor: Art Reumatoidea, Enf Autoinmune,
Nuevos antifolatos:
Pemetrexed
Expresión de RFA en cáncer
0
10
20
30
40
50
60
70
80
90
100
Ova
rian
Uterin
e
Brain/C
NSLu
ng
Kidn
ey
Head/
Neck
Breas
t
Gar
tric
Color
ecta
l
Test
icular
Endo
crine
Pamcr
eatic
% F
R E
xpre
ssio
n b
y IH
C
1. Low. Current Opin Chem Biol. 2009; 13:256-262
Positividad FRA en cáncer ovario (IHQ)
K.R. Kalli et al. / Gynecologic Oncology 108 (2008) 619–626
PRIMARY TUMOR
(72%) primary tumors
Muestra no representativa:
infraestimación
PRIMARY VS RELAPSED
K.R. Kalli et al. / Gynecologic Oncology 108 (2008) 619–626
FRA positivity at relapse
(81.5%) 22 of 27
Positividad FRA en cáncer ovario (IHQ)
B-2 What are the promising targets for future therapeutic approaches?
4th Ovarian Cancer Consensus Conference
June 25 – 27, 2010
UBC Life Sciences Institute, Vancouver, BC
• The most promising targets in clinical trials are angiogenesis and homologous
recombination deficiency.
• To select patients for trials investigating these targets, predictive biomarkers are
required. Understanding mechanisms of resistance is a priority.
• Other promising targets currently being studied based on ovarian cancer biology
include:
• PI3-Kinase and Ras/Raf pathways
• Folate receptor
• Immune targets/cytokines, Notch/hedgehog, IGF merit further investigation.
• Targeted agents should be studied both as single agents and in combination based
on appropriate preclinical data.
Resumen: por qué RFA es una diana
interesante
1) LOCALIZACIÓN TEJIDO TUMORAL (no en sano)
2) ADQUIRIDO CON LA AGRESIVIDAD cáncer ovario
ESTADÍOS AVANZADOS
ALTO GRADO
3) Modelos in vitro/ in vivo inhibición inhibe crecimiento
4) MECANISMO ENDOCITOSIS PRESERVA MOLÉCULA
ASOCIADA
RECEPTOR DE FOLATO Y CANCER
• Journal of Clinical Oncology 2013 by R. Wendel Naumann et al.
• In a randomized phase II trial the addition of vintafolide to pegylated liposomal doxorubicin improved progression-free survival in women with recurrent platinum-resistant ovarian cancer.
• PFS benefit was most marked in patients with 100% of lesions positive for folate receptors as identified by the folate receptor-targeted imaging agent 99mTc-etarfolatide.