Relief of profound feedback inhibition of mitogenic signaling by RAF inhibitors attenuates their activity in BRAFV600E melanomas. Lito P, Pratilas CA, Joseph EW, Tadi M, Halilovic E, Zubrowski M, Huang A, Wong WL, Callahan MK, Merghoub T, Wolchok JD, de Stanchina E, Chandarlapaty S, Poulikakos PI, Fagin JA, Rosen N. Cancer Cell. 2012 Nov 13;22(5):668-82. doi: 10.1016/j.ccr.2012.10.009.

RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E). Poulikakos PI, Persaud Y, Janakiraman M, Kong X, Ng C, Moriceau G, Shi H, Atefi M, Titz B, Gabay MT, Salton M, Dahlman KB, Tadi M, Wargo JA, Flaherty KT, Kelley MC, Misteli T, Chapman PB, Sosman JA, Graeber TG, Ribas A, Lo RS, Rosen N, Solit DB. Nature. 2011 Nov 23;480(7377):387-90. doi: 10.1038/nature10662.

mTOR kinase inhibition causes feedback-dependent biphasic regulation of AKT signaling. Rodrik-Outmezguine VS, Chandarlapaty S, Pagano NC, Poulikakos PI, Scaltriti M, Moskatel E, Baselga J, Guichard S, Rosen N. Cancer Discov. 2011 Aug;1(3):248-59. doi: 10.1158/2159-8290.CD-11-0085. Epub 2011 Jun 17.

Reciprocal feedback regulation of PI3K and androgen receptor signaling in PTEN-deficient prostate cancer. Carver BS, Chapinski C, Wongvipat J, Hieronymus H, Chen Y, Chandarlapaty S, Arora VK, Le C, Koutcher J, Scher H, Scardino PT, Rosen N, Sawyers CL. Cancer Cell. 2011 May 17;19(5):575-86. doi: 10.1016/j.ccr.2011.04.008.

AKT inhibition relieves feedback suppression of receptor tyrosine kinase expression and activity. Chandarlapaty S, Sawai A, Scaltriti M, Rodrik-Outmezguine V, Grbovic-Huezo O, Serra V, Majumder PK, Baselga J, Rosen N. Cancer Cell. 2011 Jan 18;19(1):58-71. doi: 10.1016/j.ccr.2010.10.031. Epub 2011 Jan 6.

4E-BP1 is a key effector of the oncogenic activation of the AKT and ERK signaling pathways that integrates their function in tumors. She QB, Halilovic E, Ye Q, Zhen W, Shirasawa S, Sasazuki T, Solit DB, Rosen N. Cancer Cell. 2010 Jul 13;18(1):39-51. doi: 10.1016/j.ccr.2010.05.023.

RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF. Poulikakos PI, Zhang C, Bollag G, Shokat KM, Rosen N. Nature. 2010 Mar 18;464(7287):427-30. doi: 10.1038/nature08902.

(V600E)BRAF is associated with disabled feedback inhibition of RAF-MEK signaling and elevated transcriptional output of the pathway. Pratilas CA, Taylor BS, Ye Q, Viale A, Sander C, Solit DB, Rosen N. Proc Natl Acad Sci U S A. 2009 Mar 17;106(11):4519-24. doi: 10.1073/pnas.0900780106. Epub 2009 Feb 27.

Basso AD, Solit DB, Munster PN, Rosen N. Ansamycin antibiotics inhibit Akt activation and cyclin D expression in breast cancer cells that overexpress HER2. Oncogene. 2002 Feb 14;21(8):1159-66.

Moasser MM, Basso A, Averbuch SD, Rosen N. The tyrosine kinase inhibitor ZD1839 (“Iressa”) inhibits HER2-driven signaling and suppresses the growth of HER2-overexpressing tumor cells. Cancer Res. 2001 Oct 1;61(19):7184-8.

Munster PN, Basso A, Solit D, Norton L, Rosen N. Modulation of Hsp90 function by ansamycins sensitizes breast cancer cells to chemotherapy-induced apoptosis in an RB- and schedule-dependent manner. Clin Cancer Res. 2001;7:2155-8.

Munster PN, Srethapakdi M, Moasser MM, Rosen N. Inhibition of heat shock protein 90 function by ansamycins causes the morphological and functional differentiation of breast cancer cells. Cancer Res. 2001 Apr 1;61(7):2945-52.

Chiosis G, Timaul MN, Lucas B, Munster PN, Zheng FF, Sepp-Lorenzino L, Rosen N. A small molecule designed to bind to the adenine nucleotide pocket of Hsp90 causes Her2 degradation and the growth arrest and differentiation of breast cancer cells. Chem Biol. 2001 Mar;8(3):289-99.

Moasser MM, Srethapakdi M, Sachar KS, Kraker AJ, Rosen N. Inhibition of Src kinases by a selective tyrosine kinase inhibitor causes mitotic arrest. Cancer Res. 1999 Dec 15;59(24):6145-52.

Zheng FF, Kuduk SD, Chiosis G, Munster PN, Sepp-Lorenzino L, Danishefsky SJ, Rosen N. Identification of a geldanamycin dimer that induces the selective degradation of HER-family tyrosine kinases. Cancer Res. 2000 Apr 15;60(8):2090-4.

Srethapakdi M, Liu F, Tavorath R, Rosen N. Inhibition of Hsp90 function by ansamycins causes retinoblastoma gene product-dependent G1 arrest. Cancer Res. 2000 Jul 15;60(14):3940-6.

Muise-Helmericks RC, Grimes HL, Bellacosa A, Malstrom SE, Tsichlis PN, Rosen N. Cyclin D expression is controlled post-transcriptionally via a phosphatidylinositol 3-kinase/Akt-dependent pathway. J Biol Chem. 1998 Nov 6;273(45):29864-72.

Stebbins CE, Russo AA, Schneider C, Rosen N, Hartl FU, Pavletich NP. Crystal structure of an Hsp90-geldanamycin complex: targeting of a protein chaperone by an antitumor agent. Cell. 1997 Apr 18;89(2):239-50.

Sepp-Lorenzino L, Ma Z, Lebwohl DE, Vinitsky A, Rosen N. Herbimycin A induces the 20 S proteasome- and ubiquitin-dependent degradation of receptor tyrosine kinases. J Biol Chem. 1995 Jul 14;270(28):16580-7.