Upon the tightrope in prostate cancer: two acrobats on the same tightrope to cross the finishline Ammad Ahmad Farooqi • Sundas Fayyaz • Sadia Rashid Received: 13 October 2011 / Accepted: 15 December 2011 / Published online: 27 December 2011 Ó Springer Science+Business Media, LLC. 2011 Abstract Prostate cancer is a multifactorial, multistep progressive disorder that is undruggable to date because of stumbling blocks in the standardization of therapy. It is triggered by a broad range of proteins, signaling networks and DNA damage response modulators. It is becoming increasingly apparent that DNA repair mediators have split personalities, as they are instrumental in suppressing and promoting carcinogenesis. In this article, we discuss on post-transcriptional processing of regulators of DNA damage response, and how DNA repair proteins trigger shuttling of androgen receptor. Substantial fraction of information has been added into the existing literature of ATM biology; however, the particular area of post-tran- scriptional processing errors and gene therapy for repro- gramming of ATM has been left unaddressed in prostate cancer. It is therefore noteworthy that the facet of targeting strategy, antisense morpholino oligonucleotides chemistry, and systematic delivery of AOs has promising outlook in splice-targeted antisense-mediated therapy. Keywords ATM Á DNA PK Á Prostate cancer Introduction Improving survival in prostate carcinogenesis is still an indefinable goal. Despite the expansion of existing land- scape of prostate cancer proteome, regarding molecular underpinnings of the disease, we are unable to witness a miscellany of novel therapeutics with reference to DNA repair proteins that are undergoing testing in clinical trials. This review mainly deals with the role of multi-talented regulators of DNA repair in suppressing and promoting cancer. We are interested in exploring how mutations of these proteins influence cellular transformation, and their crosstalks with other nuclear and cytoplasmic proteins in prostate cancer microenvironment. Prostate cancer: ATM mutations It is a well-acclaimed fact that DNA-damage–repair responses are fueled by post-translational modifications of ATM/ATR and DNA PK. Cellular responsiveness to dou- ble-strand breaks in DNA is a multipart signaling network, triggered by a protein kinase ataxia–telangiectasia mutated (ATM), which phosphorylates many downstream regula- tors at various branches of this network. Interestingly, DNA damage modulated the enhancement of the activity of ATM and simultaneously proper accumulation of ATM and downstream mediators at the sites of DNA damage. Double-stranded DNA breaks are sensed by the MRE11 complex, which triggers the activation of ATM. The MRE11 multicomponent proteome consists of meiotic recombination 11 (MRE11), RAD50, and Nijmegen breakage syndrome 1 (NBS1). Details can be found else- where [2]. Accumulating evidence indicated assorted findings of various research groups with reference to molecular epidemiological studies and suggested an A. A. Farooqi (&) Á S. Fayyaz Lab for Translational Oncology and Personalized Medicine, Rashid Latif Medical College (RLMC), 35 km Ferozepur Road, Lahore, Pakistan e-mail: Ammadahmad638@yahoo.com S. Rashid NUST Centre of Virology and Immunology (NCVI), National University of Science and Technology, Islamabad, Pakistan 123 Mol Cell Biochem (2012) 364:53–57 DOI 10.1007/s11010-011-1204-8