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Gastrointestinal Cancers (GI) Program

 

The major focus of this program is to improve staging accuracy in gastrointestinal cancers and develop innovative, more effective therapeutic strategies. To this end, multicenter clinical trials have been initiated which will provide important outcome data and this can be correlated with basic science genomic studies performed in our laboratories.

International multicenter trial to improve staging accuracy in colon cancer

In October 2008, the National Cancer Institute (NCI) approved our international trial in colon cancer. This trial went through a very stringent peer review process and involves the United States Military Cancer Institute (USMCI), Israel and Serbia. The protocol was approved in December of 2008 and has been submitted to the Institutional Review Boards (IRB) in Israel and Serbia. The overall goal of this study is to develop improved methods for staging early colon cancer and to better select candidates for postoperative chemotherapy. For some patients this will translate into a better survival while in others the toxicity and expense of chemotherapy for those patients who may already be cured can be avoided. There is a lot of interest in this study because it is the only trial that combines quality surgery, pathology and genomics in colon cancer.

Genomic analysis and gene signatures in colon cancer

By working in conjunction with ten other institutions, this trial will enable us to pursue additional hypotheses within the context of a large patient population. As a corollary to this trial, we will examine molecular characteristics of tumors to create a prognostic index based on multiple biologic specimens. These studies will be performed in our UCLA basic science laboratories. The ultimate goal of this study is to individualize patient care using the most sophisticated technology and science available.

Innovative therapeutic strategies in liver cancer

Another area of interest is pursuing our research in liver cancers. Many cancers spread to the liver and many patients succumb to liver failure. We have made significant strides in prolonging survival by developing novel surgical approaches and using these in combination with recently approved chemotherapeutic and biologic agents. At the same time we have studied mechanisms of metastases (cancer spreading) in our laboratory to identify pathways that may become targets for new therapies. This research has culminated in numerous peer-review publications.

 

 

 

 

Breast Cancer Research Program

 

In the last ten years, there have been significant advances in the treatment of breast cancer with improvements in surgery, i.e. sentinel node technology, drug therapy, i.e. Herceptin, and molecular biology with methods to identify the genetic signatures of these cancers to provide individual patient prognosis. While these advances have changed the way we stage and treat breast cancer, many patients still suffer significant morbidity and more than 30% still die from the disease.

Evaluating the Immune Environment in Breast Cancer Sentinel Lymph Nodes

While sentinel lymph node technology allows surgeons a minimally invasive method to stage the regional lymph nodes, there is little data available about the immune interactions of breast tumors and the adjacent axillary lymph nodes. Most of the emphasis of evaluating the immune response in cancer has focused on cancers such as melanoma. We propose the same principles of physical interactions of the primary tumors and regional lymph nodes seen in melanoma are applicable in breast cancer. Preliminary data from breast cancer sentinel nodes suggests that these lymph nodes are immunosuppressed similar to those found in melanoma.

We will work to understand in greater detail the process by which breast cancer escapes attack by the immune system, and how cytokines, such as IL-10, function in the spread of breast cancer to the lymph nodes. We also will work to develop methods to halt the production of immune suppressive agents as a novel approach for immune therapy for the regional lymph nodes. These experiments may lead to improved methods of boosting the patient’s own immune defenses to stop the spread of breast cancer. By producing a patient cytokine profile from the regional lymph nodes we may better define the exact cytokines are that are operative in the cancer-containing and normal lymph nodes. Also, by defining the cytokine milieu within nodes, we may be able to develop more accurate prognostic markers which can be used to test and monitor patients disease.

PET imaging for breast cancer

Whole-body positron emission tomography (PET) imaging was developed as a method to identify cancer in patients based on the relatively high uptake of the imaging agent, FDG, in tumors compared to normal tissues. In recent years PET imaging has become part of the imaging used in detecting metastatic breast cancer and now smaller imaging devices appear to have a role in detecting breast tumors not identified by other test. We have focused research on the development of a hand-held PET-sensitive probe that may help surgeons to localize breast tumors, establish the margins for tumor removal and detect the presence or absence of cancer in the regional lymph nodes. These studies will be performed to evaluate the genetic profiles of the tumors and compare to the relative uptake of FDG in the cancers. The concept is that the genetic profile of the tumors may be seen by PET imaging and the expected response to therapy could be predicted by uptake of FDG evaluated by conventional PET imaging or by use of a hand-held FDG sensitive probe used in the operating room.

In the last ten years there have been significant advances in the treatment of breast cancer with improvements in surgery, i.e. sentinel node technology, drug therapy, i.e. Herceptin, and molecular biology with methods to identify the genetic signatures of these cancers to provide individual patient prognosis. While these advances have changed the way we stage and treat breast cancer, many patients still suffer significant morbidity and more than 30% still die from the disease.

Evaluating the Immune Environment in Breast Cancer Sentinel Lymph Nodes

While sentinel lymph node technology allows surgeons a minimally invasive method to stage the regional lymph nodes, there is little data available about the immune interactions of breast tumors and the adjacent axillary lymph nodes. Most of the emphasis of evaluating the immune response in cancer has focused on cancers such as melanoma. We propose the same principles of physical interactions of the primary tumors and regional lymph nodes seen in melanoma are applicable in breast cancer. Preliminary data from breast cancer sentinel nodes suggests that these lymph nodes are immunosuppressed similar to those found in melanoma.

   
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