Nanotechnology is multidisciplinary field that involves the design and engineering of objects <500 nanometers (nm) in size. The National Cancer Institute has recognized that nanotechnology offers an extraordinary, paradigm-changing opportunity to make significant advances in cancer diagnosis and treatment. In the last several decades, nanotechnology has been studied and developed primarily for use in novel drug-delivery systems (e.g. liposomes, gelatin nanoparticles, micelles). A recent explosion in engineering and technology has led to 1) the development of many new nanoscale platforms, including quantum dots, nanoshells, gold nanoparticles, paramagnetic nanoparticles, and carbon nanotubes, and 2) improvements in traditional, lipid-based nanoscale platforms. The emerging implications of these platforms for advances in cancer diagnostics and therapeutics form the basis of this review. A widespread understanding of these new technologies is important, because they currently are being integrated into the clinical practice of oncology.

Treatment of locally advanced rectal cancer with preoperative CMT followed by TME can provide for a durable 10-year OS of 58% and RFS of 62%. Patients who achieve a >95% response to preoperative CMT have an improved long-term oncologic outcome, a novel finding that deserves further study.

Focal Adhesion Kinase (FAK) is a non-receptor kinase that is overexpressed in many types of tumors. We developed a novel cancer-therapy approach, targeting the main autophosphorylation site of FAK, Y397 by computer modeling and screening of the National Cancer Institute (NCI) small molecule compounds database. More than 140,000 small molecule compounds were docked into the Nterminal domain of the FAK crystal structure in 100 different orientations that identified 35 compounds. One compound 14 (1,2,4,5-Benzenetetraamine tetrahydrochloride) significantly decreased viability in most of the cells to the levels equal or higher than control FAK inhibitor, 1a (2-[5-Chloro-2-[2-methoxy-4-(4-morpholinyl)phenylamino]pyrimidin-4-ylamino]-Nmethylbenzamide; TAE226) from Novartis, Inc. The compound 14 specifically and directly blocked phosphorylation of Y397-FAK in a dose-and time-dependent manner. It increased cell detachment and inhibited cell adhesion in a dose-dependent manner. Furthermore, 14 effectively caused breast tumor regression in vivo. Thus, targeting the Y397 site of FAK with 14 inhibitor can be effectively used in cancer therapy.

The focal adhesion kinase (FAK) is a mediator of cellextracellular matrix signaling events and is overexpressed in tumor cells. In order to rapidly down-regulate FAK function in normal and transformed mammary cells, we have used adenoviral gene transduction of the carboxyl-terminal domain of FAK (FAK-CD). Transduction of adenovirus containing FAK-CD in breast cancer cells caused loss of adhesion, degradation of p125FAK , and induced apoptosis. Furthermore, breast tumor cells that were viable without matrix attachment also underwent apoptosis upon interruption of FAK function, demonstrating that FAK is a survival signal in breast tumor cells even in the absence of matrix signaling. In addition, both anchorage-dependent and anchorage-independent apoptotic signaling required Fas-associated death domain and caspase-8, suggesting that a death receptor-mediated apoptotic pathway is involved. Finally, FAK-CD had no effect on adhesion or viability in normal mammary cells, despite the loss of tyrosine phosphorylation of p125 FAK . These results indicate that FAKmediated signaling is required for both cell adhesion and anchorage-independent survival and the disruption of FAK function involves the Fas-associated death domain and caspase-8 apoptotic pathway.As normal epithelial cells become transformed and develop the capacity for invasion and metastasis, they must acquire the property of anchorage-independent growth. This is essential for tumor cells to survive the apoptotic stimuli associated with the loss of adhesion, proteolysis, and migration through their extracellular matrix (ECM) 1 (1, 2). Oncogenic transformation has been shown to suppress apoptosis as a means of enhancing tumor cell survival (3-6). Cells from human tumors have been shown to be more resistant to apoptotic stimuli than normal cells (7). Normal cells undergo apoptosis when they lose ECM adhesion, and this phenomenon has been termed "anoikis" (8, 9). Tumor cells have been thought to be resistant to anoikis, thus allowing them to grow in an anchorage-independent fashion. One of the critical signaling molecules involved in both cell-ECM interactions and anoikis is the focal adhesion kinase (FAK) (10), a tyrosine kinase that localizes to focal adhesions (11,12). Previous studies have shown that FAK is overexpressed in breast, colon, and thyroid cancers (13-17), whereas normal tissues express little detectable FAK. The overexpression of FAK in tumors is likely to affect three functions as follows: motility, adhesion, and survival. FAK is thought to play a role in adhesion-mediated survival because overexpression of a constitutively activated form of FAK in Madin-Darby canine kidney cells has been shown to confer resistance to apoptosis following loss of adherence (10). FAK overexpression in Chinese hamster ovary (CHO) cells caused an increase in migration (18), suggesting that FAK may play a role in motility of CHO cells. Although these experiments were performed in normal cells, they raise the possibility that tumor cells upregulate FAK expression in ord...

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