Naslov
Cancer gene therapy: a key to modulating response to anticancer therapies?

Autori
Kralj, Marijeta

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Periodicum Biologorum / Vitale, Branko - Zagreb : Hrvatsko prirodoslovno društvo, 2004, 56-56

Skup
Fourth Croatian Congres of Pharmacology with international participation

Mjesto i datum
Split, Hrvatska, 15.09.2004. - 18.09.2004

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Nije recenziran

Ključne riječi
gensko liječenje; apoptoza; kemoterapija
(gene therapy; apoptosis; chemotherapy)

Sažetak
Chemotherapy for the treatment of cancer was introduced into the clinic more than fifty years ago. This form of therapy has been successful for the treatment of many tumor types. However, the outcome of cancer treatment is often limited because of many factors, such as systemic toxicity (lack of specificity), rapid drug metabolism, and both intrinsic and acquired resistance. Since, most chemotherapy agents elicit anticancer activities by interacting with cellular proteins, damaging cellular DNA and inducing apoptosis, it is conceivable that functional levels of proteins involved in DNA synthesis and repair, apoptosis and the cell cycle will greatly affect cellular susceptibility to these agents. Apoptosis is perhaps the best studied of these cellular responses. During the past 10 years, interest of basic scientist and clinicians in the influence of apoptosis on the sensitivity of tumors to anticancer treatment has risen and continues to rise dramatically. A major reason for this interest is that apoptosis is a defined program of cell death that is markedly influenced both positively and negatively by a variety of genes, many of which are mutated and/or dysfunctionally regulated in human cancers. A detailed understanding of how anticancer agents induce cell death and how defects in apoptotic pathways promote resistance will revolutionise the way chemotherapy drugs are designed and used. One of the new approaches to therapy is to restore apoptotic potential by gene therapy. Among the most important genes that regulate the apoptotic program is the p53 gene – so called “ a master regulator” . It is capable of coordinating the process at multiple levels via several mechanisms. p53 is the most frequently mutated gene in human tumors, so loss of its function can disable apoptosis and produce multidrug resistance. Reintroduction of wild-type p53 gene in tumor cells can re-establish chemosensitivity. On the other hand, in certain circumstances apoptotic pathways may be reactivated by decreasing expression of a wide variety of antiapoptotic genes including Bcl-2, Ras, Mdm2 and Akt. Thus, improvement in gene delivery systems, and further adjuvant use of gene therapy with conventional chemotherapy, radiation therapy and surgery will all lead to better clinical responses.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

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