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Antiangiogenic therapy and tumor progression
1Brander Cancer Research Institute, New York Medical College, 19 Bradhurst Avenue, Hawthorne, NY 10532, USA. m_blagosklonny@nymc.edu
Cancer Cell
|January 30, 2004
Summary
Antiangiogenic therapy may not cause tumor progression because most cancers are already hypoxic. Successful therapy can select for resistant cancer cells, driving progression only after initial tumor regression.
Area of Science:
- Oncology
- Cancer Biology
- Tumor Microenvironment
Background:
- Angiogenesis is crucial for tumor growth, making antiangiogenic therapy a key treatment strategy.
- Hypoxia, a potential consequence of antiangiogenic therapy, is theoretically linked to increased tumor progression and metastasis.
- Conflicting views exist regarding the impact of antiangiogenic therapy-induced hypoxia on cancer aggressiveness.
Purpose of the Study:
- To reconcile the apparent contradiction between antiangiogenic therapy and tumor progression.
- To clarify the role of hypoxia in cancer aggressiveness during antiangiogenic treatment.
- To explain the conditions under which antiangiogenic therapy might select for resistant tumor phenotypes.
Main Methods:
- Literature review and theoretical analysis of existing data on tumor angiogenesis, hypoxia, and antiangiogenic therapy.
- Examination of the initial oxygenation status of tumors in relation to therapeutic interventions.
- Analysis of the selective pressures imposed by effective antiangiogenic treatments on tumor cell populations.
Main Results:
- Most tumors are not normoxic (21% O2) at the outset, suggesting that a shift to hypoxia during therapy may not activate aggressive behavior as predicted.
- Therapy-induced tumor progression is contingent upon the therapy's success in initially controlling the cancer.
- Tumor regression typically precedes the selection for and progression of therapy-resistant clones.
Conclusions:
- The notion that antiangiogenic therapy universally drives tumor progression via hypoxia needs refinement, as initial tumor conditions and therapy efficacy are critical factors.
- Successful antiangiogenic therapy can paradoxically lead to the selection of resistant cancer cells, necessitating careful monitoring and alternative treatment strategies.
- Understanding the interplay between tumor microenvironment, therapy response, and resistance mechanisms is essential for optimizing antiangiogenic treatment outcomes.