Reviews on Recent Clinical Trials - Volume 2, Issue 2, 2007

Tyrosine kinases (TK) were first described by Hunter and Cooper in the late 1970s as tyrosine-specific protein kinases encoded by transforming viruses and their normal cellular homologues [1]. Just a few years later it became already known that a number of oncogenes represented TKs [2]. It is now well known that TK are important mediators of the intracellular signaling cascade and play a key role in diverse biological proce Read More

Malignant gliomas have retained their dismal prognosis despite aggressive multimodal conventional therapeutic approaches, illustrating the need for novel therapeutic strategies. Recent advances in the cellular and molecular biology of gliomas have enhanced our understanding of the role of receptor tyrosine kinases (RTK) and RTK-mediated signal transduction pathways in tumor initiation, maintenance, angiogenesis, and vas Read More

The mammalian target of rapamycin (mTOR) kinase is positioned at the juncture of several pathways regulating cell growth and proliferation. It is the downstream effector of the oncogenic PI3K/Akt pathway and is a key regulator of translational initiation. Accumulating data support mTOR's role in lymphomagenesis, and its inhibition in preclinical models leads to lymphoma regression. The rationale for testing mTOR inhibitors Read More

The HER2/neu (HER2) gene is a member of a family of genes which has been implicated in cancer. These four genes, HER1/EGFR, HER2, HER3 and HER4 encode for transmembrane proteins that are involved in the regulation of cell proliferation, differentiation and survival. Amplification of HER2 occurs in 20%-25% of breast cancers and is associated with an aggressive tumor phenotype and poor prognosis. Results from five rando Read More

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality in the United States. Therapeutic agents that target the underlying biology of this disease are necessary to improve outcomes. Angiogenesis plays a central role in NSCLC tumor growth and metastases. The vascular endothelial growth factor pathway (VEGF) as a therapeutic target was recently validated in NSCLC. Since then, a multitude Read More

Constitutive ERK activation is a common finding in human cancer and is often the result of activating mutations of BRAF and RAS. BRAF missense mutations occur in approximately 8% of human tumors, most frequently in melanoma, papillary thyroid cancer and colon cancer. Mutations in BRAF have been found predominantly in tumors in which RAS is commonly mutated but concurrent mutations of both BRAF and RAS are extre Read More

FMS-like tyrosine kinase 3 (FLT3) is a type III receptor tyrosine kinase that is expressed on the surface of hematopoietic stem cells and plays an important role in normal hematopoiesis. FLT3 is mutated in approximately one-third of cases of acute myeloid leukemia (AML) with normal karyotype. The mutations are most commonly internal tandem duplications found in the juxtamembrane domain of the FLT3 receptor. T Read More

Receptor tyrosine kinases are a group of molecules that can enhance cellular proliferation, cell motility and migration, and eventual metastasis. c-Met receptor tyrosine kinase has a significant biological and biochemical effect on cancer cells, and appears to be an important therapeutic target. In many cancers, c-Met (which can be activated by its ligand hepatocyte growth factor, HGF) can be overexpressed, activated, amplified Read More

While CHOP has been the standard treatment for DLBL, the low cure rate of approximately 40% implies that there is a need for improvement. Several hypotheses have been tested to optimize treatment. The Goldie and Coldman hypothesis sustains that drug resistance is a function of tumor burden and, accordingly, third generation regimens were designed. A randomized trial comparing CHOP with them showed no dif Read More