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A New Player in the Development of TRAIL Based Therapies for Hepatocarcinoma Treatment: ATM Kinase
Department of Biology, University of Tor Vergata, Rome 00133, Italy
Laboratory of Cell Signaling, Santa Lucia Foundation-IRCCS, Rome 00179, Italy
* Author to whom correspondence should be addressed.
Received: 13 February 2012; in revised form: 15 March 2012 / Accepted: 26 March 2012 / Published: 5 April 2012
Abstract: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. HCCs are genetically and phenotypically heterogeneous tumors characterized by very poor prognosis, mainly due to the lack, at present, of effective therapeutic options, as these tumors are rarely suitable for radiotherapy and often resistant to chemotherapy protocols. In the last years, agonists targeting the Tumor Necrosis Factor Related Apoptosis Inducing Ligand (TRAIL) death receptor, has been investigated as a valuable promise for cancer therapy, based on their selectivity for malignant cells and low toxicity for healthy cells. However, many cancer models display resistance to death receptor induced apoptosis, pointing to the requirement for the development of combined therapeutic approaches aimed to selectively sensitize cancer cells to TRAIL. Recently, we identified ATM kinase as a novel modulator of the ability of chemotherapeutic agents to enhance TRAIL sensitivity. Here, we review the biological determinants of HCC responsiveness to TRAIL and provide an exhaustive and updated analysis of the molecular mechanisms exploited for combined therapy in this context. The role of ATM kinase as potential novel predictive biomarker for combined therapeutic approaches based on TRAIL and chemotherapeutic drugs will be closely discussed.
Keywords: ATM kinase; hepatocellular carcinoma; TRAIL; combined therapy
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Stagni, V.; Santini, S.; Barilà, D. A New Player in the Development of TRAIL Based Therapies for Hepatocarcinoma Treatment: ATM Kinase. Cancers 2012, 4, 354-378.
Stagni V, Santini S, Barilà D. A New Player in the Development of TRAIL Based Therapies for Hepatocarcinoma Treatment: ATM Kinase. Cancers. 2012; 4(2):354-378.
Stagni, Venturina; Santini, Simonetta; Barilà, Daniela. 2012. "A New Player in the Development of TRAIL Based Therapies for Hepatocarcinoma Treatment: ATM Kinase." Cancers 4, no. 2: 354-378.