research
Cell signalling in survival: Natural compounds and small-molecule inhibitors provide essential insight
- Publication date
- 28 September 2011
- Publisher
- Effective response to treatment is still a challenge in the clinical management of many types
of tumors. As result of pharmacological intervention two different fates are observed for
a cancer cell: survival or death. These two cell fates are intimately related to the overall
response to treatment. Survival of a cancer cell to an aggressive treatment usually means
inefficacy of a determined drug and cell death means that the cells were sensitive to the
treatment. In the current literature many types of cell death are suggested. Of equal
importance is the understanding of the mechanisms and signal cascades of survival.
Crosstalk between multiple signal transduction pathways may organize an intricate survival
network with overlapping functions that together provide strong survival signals to a
dying cell. Importantly, these survival signals seem to be on the background of the classic
mechanism of drug resistance which holds true for a lower efficacy of determined class of
molecules or structurally unrelated ones, such as drug efflux, drug uptake, drug metabolism,
DNA repair and impaired drug binding to its target. Importantly, different types of tumors
present different aspects of surviving, as an example the building up of a drug resistant
phenotype in hematological diseases is usually a long term process, resulting in an initial
response to treatment. However, relapses occur after sometime, and not always remission
is achieved with the same therapeutic strategy. The development or acquisition of drug
resistance is a quite remarkable aspect of hematological malignancies. On another hand,
this first response to pharmacological strategies is not really achieved in tumors such as,
pancreatic cancer (PDAC). Less than 10% of pati