Cancer therapy efficacy is often limited by toxicity in normal tissues. The ability to target chemotherapy to cancer cells, largely bypassing normal tissues, would fundamentally improve the efficacy of cancer treatment. We recently showed that a scorpion-derived peptide, chlorotoxin, targeted the near infrared fluorescent molecule, Cy5.5 to cancer cells. This new molecular imaging conjugate permitted sensitive detection of cancerous foci as small as 200 cells. Unlike most targeting agents, CTX appears to target many types of solid tumors rather than one particular type. Whereas our previous work showed that CTX:Cy5.5 is a sensitive diagnostic agent, the current proposal seeks to determine whether CTX conjugates can be used as selective therapeutic agents. The broad, long-term goal of this research is to learn how to safely use CTX to deliver cytotoxic drugs to cancer cells, thus lessening chemotherapy side effects.
The specific aims of this proposal are to 1) identify the molecular target of CTX;2) identify normal tissues that bind CTX and define CTX binding heterogeneity in selected cancers;and 3) establish the efficacy and toxicity of CTX conjugated to a potent cytotoxic drug using mouse cancer models. The significance of this work is that CTX targeting has the potential to markedly increase the therapeutic index of conjugated chemotherapy. For cancer patients, delivering higher doses of therapeutics to cancer cells while sparing most normal tissues, could result in improved survival and quality of life.

Public Health Relevance

The relevance of the proposed work is that chlorotoxin appears to be a molecule that has high potential to specifically deliver cancer therapies to cancer cells, largely bypassing normal tissues. For cancer patients, this means more therapy could be delivered to cancer cells while the patient experiences fewer side effects. Of particular interest is that chlorotoxin appears to bind to most types of malignant solid tumors rather than just one or two types.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA135491-03
Application #
7810692
Study Section
Drug Discovery and Molecular Pharmacology Study Section (DMP)
Program Officer
Fu, Yali
Project Start
2008-07-01
Project End
2013-05-31
Budget Start
2010-06-01
Budget End
2011-05-31
Support Year
3
Fiscal Year
2010
Total Cost
$365,200
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
078200995
City
Seattle
State
WA
Country
United States
Zip Code
98109
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