I. Biomarker Assay Design, Development, and ValidationWe develop, validate, and implement assays for clinical specimens using electrochemiluminescence (ECL)-based immunoassays. This is the most sensitive and quantitative immunoassay technology platform today. The ECL platform is well suited for this ongoing task because it offers a high degree of flexibility, stability and reliability. It is capable of multiplex analysis to determine the levels of total and phospho-proteins in a single assay well using a limited amount of clinical specimens. Because clinical samples may vary dramatically, the ability to normalize these samples beyond total protein concentration is critical in generating statistically significant data with patient specimens. At the present, we developed, validated and utilized a wide range of biomarker assays, including angiogenic factors, cytokines, cell surface receptors, intracellular phosphoproteins and apoptotic biomarkers. II. Recently Completed Biomarker StudiesCurrently, we are engaged with 10 clinical protocols at NCI-CCR. For many of these clinical trials, we helped to design, develop, validate, and implement customized biomarker assays for correlative analytical studies. The evaluation of these biomarkers often constitutes a pivotal part of the clinical study for investigational agents. The following are some examples in the studies that we contributed with biomarker analysis at NCI. 1.Kalra N, Zhang J, Yu Y, Ho M, Merino M, Cao L, Hassan R. Efficacy of anti-insulin-like growth factor I receptor monoclonal antibody cixutumumab in mesothelioma is highly correlated with insulin growth factor-I receptor sites/cell. International journal of cancer. 2012. 2.Speranza G, Gutierrez ME, Kummar S, Strong JM, Parker RJ, Collins J, Yu Y, Cao L, Murgo AJ, Doroshow JH, Chen A. Phase I study of the synthetic triterpenoid, 2-cyano-3, 12-dioxoolean-1, 9-dien-28-oic acid (CDDO), in advanced solid tumors. Cancer Chemother. Pharmacol. 69: 431-8, 2012. 3.Giaccone G, Rajan A, Berman A, Kelly RJ, Szabo E, Lopez-Chavez A, Trepel J, Lee MJ, Cao L, Espinoza-Delgado I, Spittler J, Loehrer PJ. Phase II Study of Belinostat in Patients With Recurrent or Refractory Advanced Thymic Epithelial Tumors. J. Clin. Oncol. 29: 2052-9, 2011. 4.Kelly RJ, Rajan A, Force J, Lopez-Chavez A, Keen C, Cao L, Yu Y, Choyke P, Turkbey B, Raffeld M, Xi L, Steinberg SM, Wright JJ, Kummar S, Gutierrez M, Giaccone G. Evaluation of KRAS Mutations, Angiogenic Biomarkers, and DCE-MRI in Patients with Advanced Non-Small-Cell Lung Cancer Receiving Sorafenib. Clin. Cancer Res. 17: 1190-9, 2011.5.Kummar S, Gutierrez ME, Chen A, Turkbey IB, Allen D, Horneffer YR, Juwara L, Cao L, Yu Y, Kim YS, Trepel J, Chen H, Choyke P, Melillo G, Murgo AJ, Collins J, Doroshow JH. Phase I trial of vandetanib and bevacizumab evaluating the VEGF and EGF signal transduction pathways in adults with solid tumours and lymphomas. Eur. J. Cancer. 47: 997-1005, 2011. III. Development of novel technology and applications with circulating tumor cellsThe ability of use circulating tumor cells (CTC) for cancer genetic and biomarker analysis offer the potential to transform clinical trials and patient management. Substantial effort was made towards CTC purification and subsequently genetic analysis of the CTC cells which results highly promising advances in this field. We have initiated 4 clinical trials in the past year with our CTC technologies, including two prove-of-concept trials with lung and prostate cancer;as well as two drug trials with a goal to provide first-of-the-kind novel enablement for using CTC to guide patient treatment. We expect to double down our effort and to have some significant advances in the near future.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Scientific Cores Intramural Research (ZIC)
Project #
1ZICBC010981-05
Application #
8554090
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2012
Total Cost
$356,520
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Strauss, Julius; Heery, Christopher R; Schlom, Jeffrey et al. (2018) Phase I Trial of M7824 (MSB0011359C), a Bifunctional Fusion Protein Targeting PD-L1 and TGF?, in Advanced Solid Tumors. Clin Cancer Res 24:1287-1295
Kang, Zhigang; Stevanovi?, Sanja; Hinrichs, Christian S et al. (2017) Circulating Cell-free DNA for Metastatic Cervical Cancer Detection, Genotyping, and Monitoring. Clin Cancer Res 23:6856-6862
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Karzai, Fatima H; Apolo, Andrea B; Cao, Liang et al. (2015) A phase I study of TRC105 anti-endoglin (CD105) antibody in metastatic castration-resistant prostate cancer. BJU Int 116:546-55
Harouaka, Ramdane; Kang, Zhigang; Zheng, Si-Yang et al. (2014) Circulating tumor cells: advances in isolation and analysis, and challenges for clinical applications. Pharmacol Ther 141:209-21
Kalra, Neetu; Zhang, Jingli; Yu, Yunkai et al. (2012) Efficacy of anti-insulin-like growth factor I receptor monoclonal antibody cixutumumab in mesothelioma is highly correlated with insulin growth factor-I receptor sites/cell. Int J Cancer 131:2143-52
Kang, Zhigang; Chen, Jun-Jie; Yu, Yunkai et al. (2011) Drozitumab, a human antibody to death receptor 5, has potent antitumor activity against rhabdomyosarcoma with the expression of caspase-8 predictive of response. Clin Cancer Res 17:3181-92
Giaccone, Giuseppe; Rajan, Arun; Berman, Arlene et al. (2011) Phase II study of belinostat in patients with recurrent or refractory advanced thymic epithelial tumors. J Clin Oncol 29:2052-9
Kummar, Shivaani; Gutierrez, Martin E; Chen, Alice et al. (2011) Phase I trial of vandetanib and bevacizumab evaluating the VEGF and EGF signal transduction pathways in adults with solid tumours and lymphomas. Eur J Cancer 47:997-1005

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