Multimodality Imaging of Tumor and Bone Response in a Mouse Model of Bony Metastasis.

Multimodality imaging of tumor and bone response in a mouse model of bony metastasis.

Filed under: Drug and Alcohol Rehabilitation

Transl Oncol. 2012 Dec; 5(6): 415-21
Hoff BA, Chughtai K, Jeon YH, Kozloff K, Galbán S, Rehemtulla A, Ross BD, Galbán CJ

Cancer drug development generally performs in vivo evaluation of treatment effects that have traditionally relied on detection of morphologic changes. The emergence of new targeted therapies, which may not result in gross morphologic changes, has spurred investigation into more specific imaging methods to quantify response, such as targeted fluorescent probes and bioluminescent cells. The present study investigated tissue response to docetaxel or zoledronic acid (ZA) in a mouse model of bony metastasis. Intratibial implantations of breast cancer cells (MDA-MB-231) were monitored throughout this study using several modalities: molecular resonance imaging (MRI) tumor volume and apparent diffusion coefficient (ADC), micro-computed tomography (µCT) bone volume, bioluminescence imaging (BLI) reporting cancer cell apoptosis, and fluorescence using Osteosense 800 and CatK 680-FAST. Docetaxel treatment resulted in tumor cell kill reflected by ADC and BLI increases and tumor volume reduction, with delayed bone recovery seen in µCT prefaced by increased osteoblastic activity (Osteosense 800). In contrast, the ZA treatment group produced similar values in MRI, BLI, and Osteosense 800 fluorescence imaging readouts when compared to controls. However, µCT bone volume increased significantly by the first week post-treatment and the CatK 680-FAST signal was slightly diminished by 4 weeks following ZA treatment. Multimodality imaging provides a more comprehensive tool for new drug evaluation and efficacy screening through identification of morphology as well as function and apoptotic signaling.
HubMed – drug

Targeted approach to metastatic colorectal cancer: what comes beyond epidermal growth factor receptor antibodies and bevacizumab?

Filed under: Drug and Alcohol Rehabilitation

Ther Adv Med Oncol. 2013 Jan; 5(1): 51-72
Troiani T, Martinelli E, Morgillo F, Capasso A, Nappi A, Sforza V, Ciardiello F

The prognosis of patients with cancer remains poor in spite of the advances obtained in recent years with new therapeutic agents, new approaches in surgical procedures and new diagnostic methods. The discovery of a plethora of cellular targets and the rational generation of selective targeting agents has opened an era of new opportunities and extraordinary challenges. The specificity of these agents renders them capable of specifically targeting the inherent abnormalities of cancer cells, potentially resulting in less toxicity than traditional nonselective cytotoxics. Among the many new types of rationally designed agents are therapeutics targeting various strategic facets of growth signal transduction, malignant angiogenesis, survival, metastasis and cell-cycle regulation. The evaluation of these agents is likely to require some changes from the traditional drug development paradigms to realize their full potential. Inhibition of the epidermal growth factor receptor and the vascular endothelial growth factor have provided proof of principle that disruption of signal cascades in patients with colorectal cancer has therapeutic potential. This experience has also taught us that resistance to such rationally developed targeted therapeutic strategies is common. In this article, we review the role of signal transduction in colorectal cancer, introduce promising molecular targets, and outline therapeutic approaches under development.
HubMed – drug

New agents on the horizon in hepatocellular carcinoma.

Filed under: Drug and Alcohol Rehabilitation

Ther Adv Med Oncol. 2013 Jan; 5(1): 41-50
Zhu AX

Despite the successful approval and extensive application of sorafenib, the prognosis for patients with advanced hepatocellular carcinoma (HCC) remains poor. Fortunately, there have been renewed and continued interests and active research in developing other molecularly targeted agents in HCC during the past few years. While there is early evidence of antitumor activity of several agents in phase I/II studies, phase III efforts with a few targeted agents have failed, highlighting the challenges of new drug development in HCC. This review summarizes the current status of other molecularly targeted agents under development in advanced HCC.
HubMed – drug

The changing landscape in the treatment of metastatic castration-resistant prostate cancer.

Filed under: Drug and Alcohol Rehabilitation

Ther Adv Med Oncol. 2013 Jan; 5(1): 25-40
El-Amm J, Aragon-Ching JB

The past few years have brought increasing advances in the therapeutic management of metastatic castration-resistant prostate cancer with the approval of several agents, including vaccine therapy with sipuleucel-T, second-line chemotherapy with cabazitaxel, the bone-targeted pharmaceutical denosumab, and the novel antiandrogen therapy abiraterone acetate. There are ongoing developments with other agents in the pipeline such as MDV3100 and alpharadin that have shown promising results. This review describes the clinical trials that brought about the drug approvals of various agents and offers some insights regarding a rational approach to optimal treatment sequencing for these drugs since national guidelines are currently lacking.
HubMed – drug

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