Pharmacological modulation of telomere length in cancer...

A - Human Necessities – 61 – K

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A61K 31/522 (2006.01)

Patent

CA 2609303

Acyclic nucleoside analogs such as acyclovir, ganciclovir, penciclovir and the corresponding pro-drugs, i.e., valacyclovir, valganciclovir and famciclovir, respectively have been identified as inhibitors or antagonists of both telomerase (encoded by TERT) and reverse transcriptase encoded by L-1 (LINE-1) RT, and as useful for treating or preventing cancers induced or mediated by the two enzymes. Method of treating or preventing such cancers in patients involves administration of a therapeutically effective amount of a composition having an inhibitor or antagonist of the reverse transcriptases in cells of the patients. The inhibitor or antagonist blocks lengthening of telomeres in telomerase positive and telomerase negative cells. Methods and kits for detecting pathologically proliferating cells expressing TERT and L1RT are also disclosed.

Selon l'invention, des analogues de nucléosides acycliques, tels que acyclovir, ganciclovir, penciclovir et les promédicaments correspondants, à savoir, valacyclovir, valganciclovir et famciclovir, ont été respectivement identifiés en tant qu'inhibiteurs ou antagonistes de la télomérase (codée par TERT) et de la transcriptase inverse codée par L-1 (LINE-1) RT, et sont utiles dans le traitement ou la prévention de cancers induits ou médiés par les deux enzymes. La méthode de traitement ou de prévention de tels cancers chez des patients implique l'administration d'une quantité efficace thérapeutiquement d'une composition possédant un inhibiteur ou un antagoniste des transcriptases inverses dans des cellules des patients. L'inhibiteur ou l'antagoniste bloque l'allongement des télomères dans des cellules télomèrase-négatives et télomèrase-positives. Ladite invention a aussi pour objet des méthodes et des kits de détection de la prolifération cellulaire pathologique exprimant TERT et L1RT.

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