Harnessing the Power of Light to See and Treat Breast Cancer

images[9]Our objective is to exploit the wealth of physiological, metabolic, morphological and molecular sources of optical contrast to develop novel strategies that focus on two breast cancer applications: tumor margin assessment and prediction of response to neo-adjuvant therapy. The proposed aims of this grant are expected to result in three major contributions. The first has the most immediate impact. An optically based strategy that can quickly and non-destructively detect positive tumor margins will decrease the need for re-excision surgery and thereby decrease the local recurrence rate and rate of distant metastases in women electing BCS. Gaining insight into the physiological, metabolic, morphological and molecular sources of heterogeneity within and among tumors and how they are modulated by therapy, drug resistance and metastatic potential will directly benefit prognostication, prediction of outcome and planning of cancer therapies. With these tools, clinicians and clinical researchers can get a better understanding of this disease and how it might react to a drug. Basic science researchers could use it as an informed approach to study tumor biology and assay the effect of novel therapeutic agents in vivo. Personal Author N. Ramanujam
For more info please go to: http://www.ntis.gov/search/product.aspx?ABBR=ADA594106 or call NTIS 1-800-553-6847 Mon – Fri 8am – 5pm est

Priming the Tumor Immune Microenvironment Improves Immune Surveillance of Cancer Stem Cells and Prevents Cancer Recurrence

images[3]Here, we report that Tumor-associated macrophages (TAMs) promote Cancer stem cell (CSC) -like phenotypes in murine breast cancer cells by up regulating their expression of Sox-2, resistance to chemotherapy, and increased tumorigenicity. Down regulation of Sox-2 in tumors blocked the ability of TAMs to induce these CSC-like phenotypes and inhibited tumor growth. We identified a novel EGFR/ Stat3/Sox-2 paracrine signaling pathway between macrophages and breast cancer cells and showed that this crosstalk was effectively blocked by small molecule inhibitors AG1478 or CDDO-Im against EGFR and Stat3, respectively. Therefore, our study identifies a novel role for TAMs in breast CSC regulation and establishes a rationale for targeting the EGFR/Stat3/Sox-2 signaling pathway for CSC therapy. Intratumoral injection of miR-19a-3p impaired the capacity of breast tumor cells to migrate and invade, suggesting it to play a critical role in induction of macrophage polarization and to be a useful therapeutic target for remodeling the tumor immune environment and thereby improve treatment of breast cancer. Personal Author R. A. Reisfeld Y. Luo For more info go to: http://www.ntis.gov/search/product.aspx?ABBR=ADA594027 or call NTIS 1-800-553-6847 Mon – Fri 8am – 5pm est

Targeted Nanoparticles for Kidney Cancer Therapy

images[2]The objective of this proposal is to test targeted carbon nanotubes for their ability to thermally ablate kidney cancer. Carbon nanotubes (CNTs) are efficient transducers of near-infrared radiation (NIR) for laser-induced thermal therapy of kidney cancer in mouse models. Our goal is to improve the anti-tumor efficacy of CNTs by designing them to target cancer cells and surrounding endothelial cells following systemic administration. Specifically, we will develop carbon nanotubes that bind to uPAR, a surface receptor overexpressed in kidney cancers and supporting endothelium. We will use D5, a peptide designed in the laboratory, as the targeting ligand. In the past year, we developed a new chemical approach to conjugating the targeting peptide to nanotubes. We demonstrated that the peptide is cytotoxic to kidney cancer cells. We also showed that the combination of nanotubes and NIR is effective in inhibiting the clonogenic survival of cultured kidney cancer cells. Next year, we will assess the flow of nanotubes in the vasculature and their ability to accumulate and exert an anti-tumor effect in a mouse tumor model. This grant is a mentor/predoctoral award that also focuses on training of a predoctoral candidate. The predoctoral fellow carried out the experiments described in this progress report, attended the national AACR cancer meeting, presented his work in seminars, and was co-first author on an article on nanotubes as thermal ablation agents.
For more into go to: http://www.ntis.gov/search/product.aspx?ABBR=ADA569286 or call NTIS 1-800-553-6847 Mon – Fri 8am – 5pm est.
Personal Author S. V. Torti