Diagnosis and Treatment: Delivering Clinical Solutions

Early detection does not guarantee a cure. And the limitations of mammography require women to undergo unnecessary biopsies and emotional strain. Ultimately patients and physicians have too few options for treatment. New breast cancer specific and individualized therapies require investigation. Lab researchers and clinicians are encouraged to engage in more cross-disciplinary research projects to link discovery efforts with the clinical issues important to breast cancer.

Two of CBCRP's Priority Issues are represented in this section:

Funding Data:

 

Proportion of CBCRP's Total

Diagnosis & Treatment grants awarded in 2002:

13

19%

Funded Amount:

$3,249,380

21%

Diagnosis & Treatment Portfolio Summary:

We are pleased that several of the newly funded grants in the Diagnosis & Treatment topics are collaborative efforts between scientists from different fields. Starting with the earliest development of the disease, Thea Tlsty at University of California, San Francisco, and Stefanie Jeffrey at Sanford University are funded for a Translational Research Collaboration award to examine the role of the connective tissues and stromal cells of the breast. Their research will examine the underlying genetic profile of tissue and cells immediately adjacent to breast tumors and pre-neoplastic lesions to see whether there are changes relative to normal stromal tissue. Detection of cancer, thus, might occur indirectly via biomarkers in the breast stroma, and this research could lead to new thinking on how breast tumors might be arrested by inhibiting the ability of non-cancerous cells to become permissive and support the tumor.

Steven Cummings, Karla Kerlikowske, and John Shepherd at the University of California, San Francisco, are funded for a Scientific Perspectives Research Collaboration exploratory award to employ novel X-ray approaches to study breast density. This project brings new technology to bear on breast cancer. This approach, if successful, also has the potential to be used as an adjunct to mammography to screen high-risk women and monitor preventive treatments. Kai Vetter and Christine Hartmann Siantar at Lawrence Livermore National Laboratory are collaborating with Gerald DeNardo at the University of California, Davis, in a TRC pilot award to develop a fundamental improvement in visualizing tumors that are "tagged" with radioactive isotopes. If successful, this approach will reduce the radiation needed and improve image quality to bring this method of diagnosis a step closer to the clinic.

Lucy Berlin with her community group, Young Moms with Breast Cancer, and Hope Rugo at the University of California, San Francisco, are sharing a Community Research Collaboration pilot award with Lynn Westphal at Stanford University. They are funded to develop a new approach to spare younger women diagnosed with breast cancer from the possible ovarian damage and infertility that often results from chemotherapy treatment. This grant is aimed at developing the information needed to advance this concept to a clinical trial. Taken together, the four collaboration awards described above allow researchers to combine critical, cross-disciplinary expertise on innovative, "high risk/high reward" projects.

Other grants funded by the CBCRP in 2002 are focused on issues related to immune therapy, new drug targets and tumor-selective agents, chemotherapy and drug resistance, and the application of novel methodologies to address treatment issues. John Reed, Xiao-Kun Zhang, and Marcia Dawson at The Burnham Institute and Francisco Piedrafita at the Sidney Kimmel Cancer Center are funded for separate innovative STEP grants to study key issues in programmed cell death (apoptosis). Breast cancer cell cells survive drug treatments, and one aspect of drug resistance is the alterations in cellular pathways that might otherwise respond to DNA damage and immune attack. Jennifer Murray at the Beckman Research Institute of the City of Hope is funded for a dissertation award to study a gene involved in expression of the key multi-drug resistance protein that often foils treatments with chemotherapy. Another dissertation award to Christine Case Lo at the University of California, San Francisco, involves the new discipline of pharmacogenomics to examine the individual response of patients to chemotherapy drugs, so that the tumor exposure and response might be optimized. Jack Youngren at the University of California, San Francisco, received funding to explore the insulin-like growth factor and small molecule inhibitors as possible anti-breast cancer agents.

Finally, two new grants focus on cell movement and angiogenesis. Clinical development of MMP (matrix metalloproteinase) inhibitors has lagged, because these enzymes are widespread in the body and have several related forms. Thus, MMP inhibitors usually have too severe side-effects that preclude clinical development. Vito Quaranta at the Scripps Research Institute will be using new CBCRP funding in collaboration with a recent Nobel Prize laureate to employ a novel chemistry method to use a specific breast cancer MMP itself to "instruct" the synthesis of a selective inhibitor. Michael Samoszuk at University of California, Irvine, is funded for to see if a normal blood clotting mechanism can be activated in the tumor blood supply to starve breast cancer.

Diagnosis & Treatment Grants Funded in 2002:

Chemotherapy-Induced Ovarian Damage: Prevention & Impact
Berlin, Lucy
Young Moms with Breast Cancer, Sunnyvale
Rugo, Hope
University of California, San Francisco
Lynn Westphal
Stanford University
Community Research Collaboration, Pilot Award
1.5 years, $82,479 (UCSF) and $52,355 (Stanford/YMBC)

Drug Dose Tailoring Based on Patient-Specific Factors
Case Lo, Christine
University of California, San Francisco
Dissertation Award
2 years, $50,572

Compositional Breast Density as a Risk Factor
Cummings, Steven; Kerlikowske, Karla; and Shepherd, John
University of California, San Francisco
Scientific Perspectives Research Collaboration, Exploratory Award
1.5 years, $100,000

Novel Retinoids with Enhanced Anti-Breast Tumor Efficacy
Dawson, Marcia
The Burnham Institute
STEP Award
2 years, $384,000

Regulation of SXR and Drug Resistance in Breast Cancer
Murray, Jennifer
Beckman Research Institute of the City of Hope
Dissertation Award
2 years, $42,784

Retinoids in Combination Therapies Against Breast Cancer
Piedrafita, Francisco
Sidney Kimmel Cancer Center
STEP Award
2 years, $396,800

MMP-Directed Synthesis of Invasive Breast Cancer Blockers
Quaranta, Vito
Scripps Research Institute
IDEA Award
1 year, $136,224

PPARγ Modulators as Apoptosis Sensitizers for Breast Cancer
Reed, John
The Burnham Institute
STEP Award
2 years, $465,373

Clotting Breast Cancer
Samoszuk, Michael
University of California, Irvine
IDEA Award
1 year, $98,986

Breast Stromal Genes Act as Early Markers of Malignancy
[Tax Check-off]
Tlsty, Thea & Jeffrey, Stefanie
University of California, San Francisco and Stanford University
Translational Research Collaboration, Full Award
3 years, $249,999 (UCSF) and $392,498 (Stanford)

New Imager to Improve Specificity in Breast Cancer Detection
Vetter, Kai; Hartmann Siantar, Christine; and DeNardo, Gerald
Lawrence Livermore National Laboratory and University of California, Davis
Translational Research Collaboration, Pilot Award
1.5 years, $213,462

Potential New Drug Therapy for Breast Cancer
Youngren, Jack
University of California, San Francisco
STEP Award
2 years, $199,848

TR3-based Peptides for Apoptosis in Breast Cancer
Zhang, Xiao-Kun
The Burnham Institute
STEP Award
2 years, $384,000

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