Abstract
Introduction:
During the past 30 years, researchers' understanding of cancer progression has
increased tremendously. This critical development has allowed for the
possibility of developing cancer chemopreventive agents. Among potential
chemopreventive agents, modalities that are already approved for cancer
treatment present the greatest potential for success, as these agents' safety
and efficacy have already been proved in cancer treatment. However,
combination therapies are now being touted as demonstrating synergistic
increases in efficacy as well as improvements in safety profiles. Although
oncology drugs are lucrative for pharmaceutical companies, the industry is
hesitant to enter the chemoprevention field because of various challenges,
including intellectual property and reimbursement issues. The development of
safe, innovative, effective drugs for cancer chemotherapy is at risk for
stagnancy if such barriers are not overcome.
Get the Answers You Need to Shape Your Strategy:
- The possible causal relationship between inflammation and cancer has been
observed in numerous malignancies. Agents that interfere with the inflammatory
process have therefore become attractive candidates upon which to base
chemopreventive strategies. Which anti-inflammatory agents are undergoing
active chemoprevention trials?
- Because many signal transduction pathways that lead to tumor growth are
also active in precancerous lesions, they, too, have become promising targets
for chemoprevention. Which of these pathway signals are already targeted by
several cancer treatments, and which treatment is currently undergoing
clinical trials specifically for cancer prevention?
- On September 13, 2007, the FDA approved Eli Lilly' s Evista for
chemoprevention of breast cancer in high-risk women. Why does Evista
represent a major advancement in the design of chemopreventive drugs?
- Clinical studies in breast and prostate cancers have yielded important
lessons in understanding the characteristics of chemopreventive agents and in
successfully designing chemopreventive trials. What lessons can be learned
from the earlier studies?
- Owing to challenges associated with transitioning cancer chemopreventive
agents to clinical use, cancer chemoprevention has received limited investment
for discovering and developing candidate agents. What challenges does
chemoprevention face? What solutions have been proposed to overcome these
challenges?
- In contrast to measuring the efficacy of well-established cardiovascular
chemopreventive agents, measuring the efficacy of an oncology chemopreventive
is extremely challenging. How can stakeholders most effectively overcome
this hurdle?
Scope:
Classes of chemopreventive agents: anti-inflammatory agents, modulators
of cancer-associated pathways, modulators of epidermal growth factor receptor
signaling pathways, modulators of TGF-beta/Smad signaling pathway, modulators
of nuclear-receptor superfamily, bioactive food components (BFCs).
Preclinical animal models: criteria for choosing an ideal animal model;
current animal models in use for evaluating cancer chemopreventive agents;
models with genetically engineered mice.
Lessons from earlier cancer chemoprevention trials: critical lessons
and guidelines to keep in mind from past breast cancer and prostate cancer
trials.
Current chemopreventive agents in development for breast cancer:
selective estrogen receptor modulators (SERMs); aromatase inhibitors;
retinoids and rexionoids; COX-2 inhibitors; combination therapy; dietary
agents.
Current chemopreventive agents in development for prostate cancer:
5-alpha-reductase inhibitors; anti-androgens; dietary agents; NSAIDs;
polyamine synthesis inhibitors; SERMs.
Challenges in chemopreventive agent development: patient-perception
barriers affecting clinical trials; reimbursement issues; intellectual
property barriers.
Opportunities: FDA-approved agents for cancer treatment; combination
therapies; strategic alliances with nutraceutical companies; biomarker
development; veterinary oncology.
Future perspectives: factors driving the development of innovative
modalities; gauging long-term safety risks; why a combination of strategies
will likely be needed to address each type of cancer malignancy; the
importance of strategic alliances.
Table of Contents
- Executive Summary
- Strategic Considerations
- Stakeholder Implications
- Overview of the Chemoprevention Strategy
- Classes of Chemopreventive Agents
- Anti-Infl ammatory Agents
- Nonspecifi c Nonsteroidal Anti-Infl ammatory Drugs
- Cyclooxygenase-2 Inhibitors
- Lipoxygenase Inhibitors
- Antimutagens
- Dithiolethiones
- Isothiocyanates
- Modulators of Cancer-Associated Pathways
- Epidermal Growth Factor Receptor
- TGFβ/Smad
- Modulators of Nuclear-Receptor Superfamily
- Bioactive Food Components
- Tea Polyphenols
- Vitamin E
- Lycopene
- Curcuminoids
- Preclinical Animal Models
- Chemoprevention Trials: Lessons from the Past
- Breast Cancer
- Prostate Cancer
- Chemopreventive Agents in Development for Breast Cancer
- Selective Estrogen Receptor Modulators
- Aromatase Inhibitors
- Retinoids
- Chemopreventive Agents in Development for Prostate Cancer
- 5-α-Reductase Inhibitors
- Selenium
- Challenges in Chemopreventive Agent Development
- Patient Perception Barriers Affecting Clinical Trial Participation
- Insurance Policy Affecting Reimbursement of Chemopreventive Agents
- Intellectual Property Barriers Affecting R&D and Investment Recovery
- Opportunities in Chemopreventive Agent Development
- FDA-Approved Agents
- EGFR Inhibitors
- HMG-CoA Reductase Inhibitors
- Angiogenesis Inhibitors
- Matrix Metalloproteinases
- Combination Therapies
- Strategic Alliances with Nutraceutical Companies
- Biomarker Development
- Veterinary Oncology
- Future Perspectives
Tables
- 1. Classes of Potential Chemopreventive Agents
- 2. Potential Chemopreventive Bioactive Food Components
- 3. Animal Models for the Screening and Development of Chemopreventive
Agents
- 4. Chemopreventive Agents and Related Clinical Trials for Breast Cancer
- 5. Chemopreventive Agents and Related Clinical Trials for Prostate Cancer
- 6. Key Challenges and Proposed Solutions for Chemopreventive Agent
Development
- 7. Potential Chemopreventive Molecular Targets and Agents
Figures
- 1. Carcinogenesis and Chemoprevention
