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TRATAMIENTO ONCOLOGICO NO RADICAL DIRIGIDO AL ESTROMA

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La administración diaria de una dosis baja de agentes citotóxicos, denominada quimioterapia metronómica, mostró también efectos antiangiógenos y, por lo tanto, podría complementar las nuevas estrategias dirigidas al estroma que utilizan biomoduladores.
bundscherer9.jpg Autor:
Annika Bundscherer
Columnista Experto de SIIC
Artículos publicados por Annika Bundscherer
Coautores
Christian Hafner* Thomas Vogt* 
MD, University of Regensburg, Regensburg, Alemania*
Recepción del artículo
30 de Noviembre, 2006 		Aprobación
6 de Febrero, 2007
Primera edición
3 de Agosto, 2007 		Segunda edición, ampliada y corregida
7 de Junio, 2021

TRATAMIENTO ONCOLOGICO NO RADICAL DIRIGIDO AL ESTROMA

Resumen
El tratamiento del cáncer refractario a la quimioterapia y metastásico sigue siendo un gran desafío en oncología. La terapia convencional del cáncer consiste en cirugía, quimioterapia cíclica con las dosis máximas toleradas y radioterapia. Aunque los efectos iniciales de estos regímenes a menudo son muy impresionantes, la selección de clones tumorales resistentes suele conducir a la progresión de la enfermedad. Además, la quimioterapia convencional puede asociarse con efectos colaterales graves y limitantes de la dosis. En la búsqueda de nuevas estrategias para el tratamiento oncológico no radical, las dirigidas al estroma y las antiangiógenas representan actualmente novedosas alternativas potencialmente útiles. Es interesante señalar que varios fármacos bien conocidos que se encuentran en uso clínico para indicaciones no oncológicas también muestran efectos sobre el estroma tumoral. Por ejemplo, se demostró que agentes como los antagonistas de mTOR, los agonistas de PPAR-γ y los inhibidores de la COX-2 inducen apoptosis e inhiben la proliferación celular en las células tumorales, lo cual está más allá de su campo de aplicación. Cabe señalar que además de distintas actividades antineoplásicas, estos agentes pueden mostrar efectos antiangiógenos e inmunomoduladores al interferir con la interacción tumor-estroma. El uso combinado de estos agentes biomoduladores podría conducir a efectos antitumorales sinérgicos sin provocar efectos colaterales graves. Más aun, la administración diaria de una dosis baja de los agentes citotóxicos, denominada quimioterapia metronómica, mostró también efectos antiangiógenos y, por lo tanto, podría complementar a las nuevas estrategias que utilizan biomoduladores dirigidas al estroma. En concordancia ya se demostró en varios estudios preclínicos la eficiencia antitumoral del uso combinado de los agentes biomoduladores y la quimioterapia metronómica. Los nuevos resultados de los ensayos clínicos que se encuentran en progresión estimularán el desarrollo de estas estrategias dirigidas al estroma.

Palabras clave
terapia dirigida contra el estroma, quimioterapia metronómica, antagonistas mTOR, agonistas PPAR (gamma), inhibidores de la COX-2


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Stroma-Targeted Therapy: An Emerging New Concept in Tumor Palliation

Abstract
The treatment of chemorefractory and metastatic cancer remains to be a great challenge in oncology. Conventional cancer therapy consists of surgery, cyclic chemotherapy with maximal tolerated doses and radiotherapy. Although the initial effects of these regimen are often quite impressive, selection of resistant tumor clones often leads to progression of disease. Furthermore, conventional chemotherapy can be associated with severe and dose limiting side effects. In search for new strategies for tumor palliation, stroma targeted and antiangiogenetic strategies now are emerging potentially useful alternatives. Interestingly, several well established drugs, which are in clinical use for non-oncological indications, also exhibit effects on the tumor stroma. For instance agents such as mTOR antagonists, PPAR-γ agonists and COX 2 inhibitors were shown to induce apoptosis and inhibit cell proliferation in tumor cells beyond their primary field of application in medicine. Notably, in addition to direct anticancer activities, these drugs are able to exhibit antiangiogenetic and immunmodulating effects by interfering with the tumor-stroma interaction. Combinatorial use of these biomodulating agents might lead to super-additive antitumor effects without causing severe side effects. Moreover, daily low dose administration of cytotoxic drugs, referred to as metronomic chemotherapy, turned out to exhibit antiangiogenetic effects as well and may thereby complement the novel strategies using biomodulators for stroma targeting. Accordingly, in several preclinical studies, the antitumoral efficiency of combinatorial use of both biomodulating drugs and metronomic chemotherapy has already been demonstrated. New results of ongoing clinical trials will encourage the developing of such stroma-targeted therapies.

Key words
stroma-targeted therapy, metronomic chemotherapy, mTOR antagonists, PPAR(gamma) agonists, COX 2 inhibitors


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Especialidades
Principal: Oncología
Relacionadas: Bioética, Farmacología, Medicina Farmacéutica, Medicina Interna



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Enviar correspondencia a:
Thomas Vogt, Department of Dermatology, University of Regensburg , D-93042, Franz-Josef- Strauß Allee 11, Regensburg, Alemania
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