RT Journal Article
ID 756bfbeb6a585101
A1 Nonnenmacher, Lisa
A1 Hasslacher, Sebastian
A1 Zimmermann, Julia
A1 Karpel-Massler, Georg
A1 La Ferla-Brühl, Katia
A1 Barry, Sara E.
A1 Burster, Timo
A1 Siegelin, Markus D.
A1 Brühl, Oliver
A1 Halatsch, Marc-Eric
A1 Debatin, Klaus-Michael
A1 Westhoff, Mike-Andrew
T1 Cell Death Induction in Cancer Therapy − Past, Present, and Future
JF Critical Reviews™ in Oncogenesis
JO CRO
YR 2016
FD 2016-10-24
VO 21
IS 3-4
SP 253
OP 267
K1 apoptosis
K1 cancer therapy
K1 Darwinian principles
K1 tumor ecosystem
K1 therapeutic endpoints
AB The induction of apoptosis, a physiological type of cell death, is currently the primary therapeutic aim of most
cancer therapies. As resistance to apoptosis is an early hallmark of developing cancer, the success of this treatment strategy is already potentially compromised at treatment initiation. In this review, we discuss the tumor in Darwinian terms and describe it as a complex, yet highly unstable, ecosystem. Current therapeutic strategies often focus on directly killing the dominant subclone within the population of mutated cancer cells while ignoring the subclonal complexity within the ecosystem
tumor, the complexity of the direct tumor/ microenvironment interaction and the contribution of the ecosystem human − that
is, the global environment which provides the tumor with both support and challenges. The Darwinian view opens new possible therapeutic interventions, such as the disruption of the microenvironment by targeting nonmutated cells within the tumor or the interaction points of mutant tumor cells with their environment, and it forces us to reevaluate therapeutic endpoints. It is our belief that a central future challenge of apoptosis-inducing therapies will be to understand better under which preconditions which treatment strategy and which therapeutic endpoint will lead to the highest quality and quantity of a patient's life.
PB Begell House
LK https://www.dl.begellhouse.com/journals/439f422d0783386a,5c1116ad47548349,756bfbeb6a585101.html