Tumor angiogenesis factor. Speculations on an approach to cancer chemotherapy.

Abstract

Tumor angiogenesis factor (TAF) and its importance in determining a strategy for cancer chemotherapy are discussed. It is suggested that inhibition of RNA synthesis or increased RNA catabolism might interfere with the metabolism of solid tumor cells more so than in normal cells, and thus hinder angiogenesis and pursuant tumor growth by preventing the synthesis of the RNA component of TAF. An attempt is made to indicate potential models for anti-angiogenesis agents of this type. The drugs offered as initial prototypes for investigations along these lines are actinomycin D (which likely has antimetabolite and anti-angiogenesis activities), polyriboinosinic-polyribocytidylic acid (which likely has adjuvant and anti-angiogenesis activities) and ribonuclease (which in theory might be a purely anti-angiogenetic agent). It is noted that these models may turn out to be less than ideal as therapeutic agents due to problems of toxicity, metabolism, potency, or distribution, but nonetheless might serve to yield insights into the design of new cancer chemotherapeutic drugs. In addition, some evidence is cited suggesting that actinomycin D may be more effective against certain tumors when employed in lower, chronic dosages rather than its present use in "loading" dosages.The concept of anti-angiogenesis agents as fundamentally "tumoristatic" therapies is discussed, and the likelihood that such agents might be effectively "tumoricidal" in immunocompetent hosts is mentioned. The main promise of an anti-angiogenetic strategy is efficacy against presently intractable slowly growing human cancers when used in combination with other treatment modalities. In summary, a strategy of cancer chemotherapy predicated upon interference with RNA synthesis or increase in RNA catabolism is offered as a potential mechanism for establishing anti-angiogenesis, and as a promising alternative and adjunct to present methods.

• Authors: N Blumberg
• Journal: The Yale journal of biology and medicine (Yale J Biol Med) Vol. 47 Issue 2 Pg. 71-81 ( 1974) ISSN: 0044-0086 [Print] United States
• PMID: 4139828 (Publication Type: Journal Article, Review)

Chemical References

• Antineoplastic Agents
• RNA, Neoplasm
• Dactinomycin
• Ribonucleases
• Poly I-C

Topics

• Antineoplastic Agents (therapeutic use)
• Dactinomycin (pharmacology, therapeutic use)
• Humans
• Models, Biological
• Neoplasms (blood, drug therapy, metabolism)
• Poly I-C (pharmacology, therapeutic use)
• RNA, Neoplasm (antagonists & inhibitors, biosynthesis, metabolism)
• Ribonucleases (pharmacology, therapeutic use)
• Time Factors