The current knowledge on molecular mechanisms of apoptosis is presented focusing on the key elements of the extrinsic death receptor pathway as well as the intrinsic mitochondrial pathway. Disregulation of apoptotic pathways is considered as a key factor in the survival of cancer cells in response to conventional chemotherapeutic drugs or radiation therapy. Substances that selectively reactivate apoptosis in malignant cells are the promising candidate anticancer drugs, which have now entered various phases of clinical trials. The up-to-date techniques allowing for non-invasive in vivo visualization of apoptotic cells with special reference to therapy-induced cell death are briefly surveyed.
Download PDF:
Keywords: apoptosis, targeted therapy, cancer patients, clinical trials, single photon emission computed tomography, positron emission tomography, extracellular markers of apoptosis
Kartachova M.S., Valdes Olmos R.A., Haas R.L., Hoebers F.J., van Herk M., Verheij M. (2008) Nucl. Med. Commun., 29, 39-44. CrossRef Scholar google search
Reshef A., Shirvan A., Akselrod-Ballin A., Wall A., Ziv I. (2010) J. Nucl. Med., 51, 837-840. CrossRef Scholar google search
Pennarun B., Meijer A., de Vries E.G., Kleibeuker J.H., Kruyt F., de Jong S. (2010) Biochim. Biophys. Acta, 1805, 123-140. Scholar google search
Elias A., Siegelin M.D., Steinmueller A., von Deimling A., Lass U., Korn B., Mueller W. (2009) Clin. Cancer Res., 15, 5457-5465. CrossRef Scholar google search
Pal R., Srivastava N., Chopra R., Gochhait S., Gupta P., Prakash N., Agarwal G., Bamezai R.N. (2010) Mol. Cancer, 9, 303. CrossRef Scholar google search
Chamuleau M.E., Ossenkoppele G.J., van Rhenen A., van Dreunen L., Jirka S.M., Zevenbergen A., Schuurhuis G.J., van de Loosdrecht A.A. (2011) Leuk. Res., 35, 741-749. CrossRef Scholar google search
Tamm I., Kornblau S.M., Segall H., Krajewski S., Welsh K., Kitada S., Scudiero D.A., Tudor G., Qui Y.H., Monks A., Andreeff M., Reed J.C. (2000) Clin. Cancer Res., 6, 1796-1803. Scholar google search
Marusawa H., Matsuzawa S., Welsh K., Zou H., Armstrong R., Tamm I., Reed J.C. (2003) EMBO J., 22, 2729-2740. CrossRef Scholar google search
Soria J.C., Smit E., Khayat D., Besse B., Yang X., Hsu C.P., Reese D., Wiezorek J., Blackhall F. (2010) J. Clin. Oncol., 28, 1527-1533. CrossRef Scholar google search
Maddipatla S., Hernandez-Ilizaliturri F.J., Knight J., Czuczman M.S. (2010) Clin. Cancer Res., 13, 4556-4564. CrossRef Scholar google search
Tolcher A.W., Mita M., Meropol N.J., von Mehren M., Patnaik A., Padavic K., Hill M., Mays T., McCoy T., Fox N.L., Halpern W., Corey A., Cohen R.B. (2007) J. Clin. Oncol., 25, 1390-1395. CrossRef Scholar google search
Hotte S.J., Hirte H.W., Chen E.X., Siu L.L., Le L.H., Corey A., Iacobucci A., MacLean M., Lo L., Fox N.L., Oza A.M. (2008) Clin. Cancer Res., 14, 3450-3455. CrossRef Scholar google search
Wakelee H.A., Patnaik A., Sikic B.I., Mita M., Fox N.L., Miceli R., Ullrich S.J., Fisher G.A., Tolcher A.W. (2010) Ann. Oncol., 21, 376-381. CrossRef Scholar google search
Herbst R.S., Kurzrock R., Hong D.S., Valdivieso M., Hsu C.P., Goyal L., Juan G., Hwang Y.C., Wong S., Hill J.S., Friberg G., LoRusso P.M. (2010) Clin. Cancer Res., 16, 5883-5891. CrossRef Scholar google search
Camidge D.R., Herbst R.S., Gordon M.S., Eckhardt S.G., Kurzrock R., Durbin B., Ing J., Tohnya T.M., Sager J., Ashkenazi A., Bray G., Mendelson D. (2010) Clin. Cancer Res., 16, 1256-1263. CrossRef Scholar google search
Greco F.A., Bonomi P., Crawford J., Kelly K., Oh Y., Halpern W., Lo L., Gallant G., Klein J. (2008) Lung Cancer, 61, 82-90. CrossRef Scholar google search
Trarbach T., Moehler M., Heinemann V., Koehne C.H., Przyborek M., Schulz C., Sneller V., Gallant G., Kanzler S. (2010) Br. J. Cancer, 102, 506-512. CrossRef Scholar google search
Younes A., Vose J.M., Zelenetz A.D., Smith M.R., Burris H.A., Ansell S.M., Klein J., Halpern W., Miceli R., Kumm E., Fox N.L., Czuczman M.S. (2010) Br. J. Cancer, 103, 1783-1787. CrossRef Scholar google search
Mom C.H., Verweij J., Oldenhuis C.N., Gietema J.A., Fox N.L., Miceli R., Eskens F.A., Loos W.J., de Vries E.G., Sleijfer S. (2009) Clin. Cancer Res., 15, 5584-5590. CrossRef Scholar google search
Stern H.M., Padilla M., Wagner K., Amler L., Ashkenazi A. (2010) Clin. Cancer Res., 16, 1587-1596. CrossRef Scholar google search
Walczak H., Miller R.E., Ariail K., Gliniak B., Griffith T.S., Kubin M., Chin W., Jones J., Woodward A., Le T., Smith C., Smolak P., Goodwin R.G., Rauch C.T., Schuh J.C., Lynch D.H. (1999) Nat. Med., 5, 157-163. CrossRef Scholar google search
Liu G., Kelly W.K., Wilding G., Leopold L., Brill K., Somer B. (2009) Clin. Cancer Res., 15, 3172-3176. CrossRef Scholar google search
Ready N., Karaseva N.A., Orlov S.V., Luft A.V., Popovych O., Holmlund J.T., Wood B.A., Leopold L. (2011) J. Thorac. Oncol., 6, 781-785. CrossRef Scholar google search
Talbot D.C., Ranson M., Davies J., Lahn M., Callies S., Andre V., Kadam S., Burgess M., Slapak C., Olsen A.L., McHugh P.J., de Bono J.S., Matthews J., Saleem A., Price P. (2010) Clin. Cancer Res., 16, 6150-6158. CrossRef Scholar google search
Dean E., Jodrell D., Connolly K., Danson S., Jolivet J., Durkin J., Morris S., Jowle D., Ward T., Cummings J., Dickinson G., Aarons L., Lacasse E., Robson L., Dive C., Ranson M. (2009) J. Clin. Oncol., 27, 1660-1666. CrossRef Scholar google search
Carrasco R.A., Stamm N.B., Marcusson E., Sandusky G., Iversen P., Patel B.K. (2011) Mol. Cancer Ther., 10, 221-232. CrossRef Scholar google search
Roedel F., Frey B., Leitmann W., Capalbo G., Weiss C., Roedel C. (2008) Int. J. Radiat. Oncol. Biol. Phys., 71, 247-255. CrossRef Scholar google search
Kluger H.M., McCarthy M.M., Alvero A.B., Sznol M., Ariyan S., Camp R.L., Rimm D.L., Mor G. (2007) J. Transl. Med., 5, 6. CrossRef Scholar google search
Silasi D.A., Alvero A.B., Rutherford T.J., Brown D., Mor G. (2009) Expert Opin. Pharmacother., 10, 1059-1067. CrossRef Scholar google search
Nemunaitis J., Clayman G., Agarwala S.S., Hrushesky W., Wells J.R., Moore C., Hamm J., Yoo G., Baselga J., Murphy B.A., Menander K.A., Licato L.L., Chada S., Gibbons R.D., Olivier M., Hainaut P., Roth J.A., Sobol R.E., Goodwin W.J. (2009) Clin. Cancer Res., 15, 7719-7725. CrossRef Scholar google search
Swisher S.G., Roth J.A., Komaki R. et al. (2003) Clin. Cancer Res., 9, 93-101. Scholar google search
Yoo G.H., Moon J., Leblanc M., Lonardo F., Urba S., Kim H., Hanna E., Tsue T., Valentino J., Ensley J., Wolf G. (2009) Arch. Otolaryngol. Head Neck Surg., 135, 869-874. CrossRef Scholar google search
Blankenberg F.G., Katsikis P.D., Tait J.F., Davis R.E., Naumovski L., Ohtsuki K., Kopiwoda S., Abrams M.J., Darkes M., Robbins R.C., Maecker H.T., Strauss H.W. (1998) Proc. Natl. Acad. Sci. USA, 95, 6349-6354. CrossRef Scholar google search
Kemerink G.J., Liem I.H., Hofstra L., Boersma H.H., Buijs W.C., Reutelingsperger C.P., Heidendal G.A. (2001) J. Nucl. Med., 42, 382-387. Scholar google search
Belhocine T., Steinmetz N., Hustinx R., Bartsch P., Jerusalem G., Seidel L., Rigo P., Green A. (2002) Clin. Cancer Res., 8, 2766-2774. Scholar google search
Kartachova M., van Zandwijk N., Burgers S., van Tinteren H., Verheij M., Valdes Olmos R.A. (2007) J. Clin. Oncol., 25, 2534-2539. CrossRef Scholar google search