Molecular-targeted therapies

In this emerging era of molecular-targeted therapies, biomarkers are becoming more useful and perhaps even necessary for the success of new drugs. In this context, the two classes of biomarkers that are most relevant are pharmacodynamic biomarkers, which are used to confirm drug activity and mechanism of action, and predictive biomarkers, which are used to predict clinical response to targeted therapies. 

One of the most exciting areas of combined modality therapy is the specific molecular targeted therapy in combination with radiation. Over the past decade there has been a quantum increase in the understanding of molecular mechanisms that underlie the process of tumor development, proliferation, invasion, and metastasis. 

Haber DA, Bell DW, Sordella R et al. Molecular targeted therapy of lung cancer EGFR mutations and response to EGFR inhibitors. Cold Spring Harb Symp Quant Biol 2005 70 419-426. 

Deininger MW. Basic science going clinical molecularly targeted therapy of chronic myelogenous leukemia. J Cancer Res Clin Oncol 2004 130 59-72. 

Pathological Research on Molecular-Targeted Therapy and Advanced ImmunohistochemicalApproaches... 

THE CHALLENGE — MOLECULARLY TARGETED THERAPIES AND NEW PARADIGMS FOR CLINICAL TRIALS... 

Rosa DD, Ismael G, Lago LD, et al. Molecular-targeted therapies Lessons from years of clinical development. Cancer Treat Rev. 2008 34(l) 61-80. 

Protein Cooperativity and Wrapping Two Themes in the Transformative Platform of Molecular Targeted Therapy... 

These are all crucial problems in molecular targeted therapy that will be addressed in the subsequent chapters as we assess the transformative power of the wrapping concept. 

Wrapping as a Selectivity Filter for Molecular Targeted Therapy Preliminary Evidence... 

Druker BJ (2004) Molecularly targeted therapy Have the floodgates opened Oncologist 9 357-360... 

Context-dependent functionalities introduce a risk of toxicity in molecular target therapy [4-7], For example, the constitutively active chimera Bcr-ABL kinase is a clinical target for treating chronic myeloid leukemia (CML), as evidenced by the success of the KI imatinib (Gleevec) [18], but ABL inhibition in cardiomyocytes (off-target cells in CML treatment) may introduce a cardiotoxicity risk [5-7], as shown in Fig. 12.1. This risk is more pronounced for promiscuous KIs like sunitinib [5, 8],... 

Widakowich C, de Castro G, de Azambuja E, Dinh P, Awada A (2007) Review Side effects of approved molecular targeted therapies in solid cancers. Oncologist 12 1443-1455... 

Therapy of both ALL and AML are based on specific risk factors such as age or WBC count at time of diagnosis in ALL. For both ALL and AML, cytogenetic abnormalities provide significant information regarding risk stratification and identify subgroups that may benefit from novel molecularly targeted therapies. 

CD20 is the target for Rituxan, the anti-CD20 molecular targeted therapy for CD20 positive lymphomas. This is a common theranostic use for lymphoma patients, as well as for patients with rheumatoid arthritis. 

Kondapalli L, Soltani K, Lacoumre ME. The promise of molecular targeted therapies protein kinase inhibitors in the treatment of cutaneous malignancies. J Am Acad Dermatol. 2005 53 291-302. 

Llovet JM, Bruix J. Molecular targeted therapies in hepatocellular carcinoma. Hepatology. 2008 48 1312-1327. 

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