Apoptosis: a relevant tool for anticancer therapy.
Apoptosis is a form of cell death that permits the removal of damaged, senescent or unwanted cells in multicellular organisms, without damage to the cellular microenvironment. Defective apoptosis represents a major causative factor in the development and progression of cancer. The majority of chemotherapeutic agents, as well as radiation, utilize the apoptotic pathway to induce cancer cell death. Resistance to standard chemotherapeutic strategies also seems to be due to alterations in the apoptotic pathway of cancer cells. Recent knowledge on apoptosis has provided the basis for novel targeted therapies that exploit apoptosis to treat cancer. These new target include those acting in the extrinsic/intrinsic pathway, proteins that control the apoptosis machinery such as the p53 and proteosome pathway. Most of these forms of therapy are still in preclinical development because of their low specifity and susceptibility to drug resistance, but several of them have shown promising results. In particular, this review specifically aims at providing an update of certain molecular players that are already in use in order to target apoptosis (such as bortezomib) or which are still being clinically evaluated (such ONYX-015, survivin and exisulind/aptosyn) or which, following preclinical studies, might have the necessary requirements for becoming part of the anticancer drug programs (such as TRAIL/Apo2L, apoptin/VP3).
Russo
A
A
Section of Medical Oncology, Department of Surgical and Oncology, Università di Palermo, Italy. lab-oncobiologia@usa.net
Terrasi
M
M
Agnese
V
V
Santini
D
D
Bazan
V
V
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001897:Boronic Acids / Q000494:pharmacology; D000069286:Bortezomib; D036022:Capsid Proteins / Q000494:pharmacology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008024:Ligands; D008869:Microtubule-Associated Proteins / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000494:pharmacology; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D011719:Pyrazines / Q000494:pharmacology; D053218:Receptors, Death Domain / Q000378:metabolism; D013467:Sulindac / Q000031:analogs & derivatives / Q000494:pharmacology; D000077022:Survivin; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology
D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D001897:Boronic Acids; D036022:Capsid Proteins; D051034:Inhibitor of Apoptosis Proteins; D008024:Ligands; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011719:Pyrazines; D053218:Receptors, Death Domain; D000077022:Survivin; D053221:TNF-Related Apoptosis-Inducing Ligand; C091717:VP3 protein, Chicken anemia virus; D013467:Sulindac; D000069286:Bortezomib; C025463:sulindac sulfone