First international conference on new molecular targets for anticancer therapy, Naples, 22-23 June 1998.
The First International Conference on New Molecular Targets for Anticancer Therapy was held in Naples on 22-23 June 1998, and represented an excellent occasion for discussing ongoing preclinical and clinical studies in the field of angiogenesis, signal transduction and antisense. In two general lectures, early clinical trials which are ongoing at EORTC and NCI, Bethesda, were summarized. Neoangiogenesis has been considered as a central pathogenic step in the process of tumor growth, invasion and metastasis. This complex process involves multiple steps and pathways dependent on the local balance between positive and negative regulatory factors, as well as interaction between the tumor, its vasculature and the surrounding extracellular matrix. Therapeutic agents and strategies are currently being devised to block one or more of the pathogenic steps involved in the process of tumor neovascularization or to directly target and destroy tumor vasculature. Since aberrant cell signaling plays a key role in the initiation, growth and progression of many tumors, signal transduction inhibitors may have a role as cytostatic agents. In addition, cancer sensitivity/resistance to conventional chemo/radiotherapy is largely dependent on cell signaling; hence its inhibition may induce a fundamental shift towards sensitivity. Thus, signal transduction inhibitors may play an important role also as modulators of conventional therapies, by shifting the balance towards pro-apoptotic signaling. Modulation of gene expression using oligonucleotides is currently an area of intense preclinical and clinical investigation. The effectiveness of antisense oligonucleotides as therapeutic agents depends, in addition to biological activity, on pharmacokinetics, tissue disposition, in vivo metabolic activity, elimination and safety profile. Probably the most clever way of using antisense oligonucleotides is to combine them with conventional chemotherapy, exploiting the different and possibly complementary mechanisms of action of the two treatment modalities.
Budillon
A
A
Divisione di Oncologia Sperimentale C, Istituto Nazionale Tumori, Fondazione G Pascale, Napoli, Italy.
Caponigro
F
F
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D002986:Clinical Trials as Topic; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D016372:RNA, Antisense / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects*
D000970:Antineoplastic Agents; D016372:RNA, Antisense