Methods of diagnosing, prognosing and treating breast cancer

A - Human Necessities – 61 – K

Patent

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A61K 48/00 (2006.01) C12N 5/09 (2010.01) C12N 15/113 (2010.01) A61K 31/138 (2006.01) A61K 31/4535 (2006.01) A61K 31/7068 (2006.01) A61K 31/7088 (2006.01) A61K 31/7105 (2006.01) A61K 39/395 (2006.01) A61P 35/00 (2006.01) C12N 15/00 (2006.01) C12Q 1/68 (2006.01)

Patent

CA 2526862

The protein pRb2/p130 represses expression of the ER-.alpha. gene. Blocking pRb2/p130 expression or altering ER-.alpha. gene methylation to alter pRb2/p130 complex binding allows transcriptional activity of the ER-.alpha. gene to be restored. Detecting and regulating the methylation state of the ER- .alpha. gene, optionally together with detecting and regulating pRb2/p130 multimolecular complexes bound to the ER-.alpha. gene promoter, allows estrogen-insensitive breast cancer cells to be identified, so that an accurate prognosis can be obtained and an appropriate course of treatment administered. Also, inhibiting pRb2/p130, or altering the methylation pattern of the ER- .alpha. gene by targeting DNMT 1 I n the pRb2/p 130-E2F4/5-HDAC 1-DNMT1- SUV39H1 complex, allows estrogen-insensitive breast cancer cells to be converted to estrogen-sensitive breast cancer cells. Estrogen-sensitive breast cancer cells which are generally more susceptible to current anti-cancer treatments.

L'invention porte sur la protéine pRb2/p130 qui refoule l'expression du gène ER-.alpha., ainsi que sur le blocage de l'expression par pRb2/p130 ou la modification de la méthylation du gène ER-.alpha. visant à modifier la liaison du complexe de pRb2/p130, ce qui permet de rétablir l'activité transcriptionnelle du gène ER-.alpha.. L'invention porte également sur la détection et la régulation de l'état de méthylation du gène ER-.alpha., associées éventuellement à la détection et à la régulation des complexes multimoléculaires de pRb2/p130 qui sont liées au promoteur du gène ER-.alpha., ce qui permet d'identifier des cellules du cancer du sein insensibles aux oestrogènes et d'obtenir un pronostic précis du cours du traitement approprié, administré. L'invention porte également sur l'inhibition de pRb2/p130 ou sur la modification du schéma de méthylation du gène ER-.alpha. qui consistent à cibler DNMT 1 I sur le complexe pRb2/p 130-E2F4/5-HDAC 1-DNMT1-SUV39H1, ce qui permet de convertir les cellules du cancer du sein insensibles aux oestrogènes en cellules sensibles. Les cellules du cancer du sein sensibles aux oestrogènes réagissent généralement mieux aux traitements anticancéreux courants.

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