Related Experiment Video
Updated: Feb 1, 2026
Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
Published on: September 19, 2018
[Drug resistance mediated by survival- and growth-promoting signaling pathways]
1Division of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan.
Abstract:
The serine/threonine kinases, Akt and Pim, are key molecules for cell signaling downstream of growth factors, cytokines and other stimuli. Akt and Pim kinases regulate cellular processes that are associated with the aggressiveness of a number of different cancers. They protect cells from undergoing apoptosis and promote cell growth by phosphorylating their downstream substrates, which lead to the occurrence of resistance to anti-cancer drugs and radiation. Activation of Akt and Pim by transfecting their expression plasmids or by modulating their regulators attenuated the cytotoxic effects of anti-tumor drugs. Thus, the pathways are attractive targets for enhancing the sensitivity to and overcoming resistance to anti-cancer drugs. Recently, several small molecular inhibitors targeting the components of the Akt and Pim signaling pathways have been developed, and some inhibitors have already entered clinical trials. Further, some interesting associated proteins and substrates of the pathways have been identified. In future, new therapy targeting Akt and Pim signaling pathways will be developed to selectively induce apoptosis in cancer cells and to overcome drug resistance.
Insights
Akt and Pim kinases promote cancer growth and drug resistance by regulating cell survival. Targeting these pathways with new inhibitors offers a promising strategy to enhance anti-cancer drug efficacy and overcome resistance.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- Akt and Pim kinases are crucial signaling molecules activated by various stimuli.
- These kinases regulate cell survival, growth, and are implicated in cancer aggressiveness.
- They contribute to resistance against chemotherapy and radiation therapy.
Purpose of the Study:
- To highlight the role of Akt and Pim signaling in cancer.
- To discuss their involvement in drug resistance.
- To explore therapeutic strategies targeting these pathways.
Main Methods:
- Review of existing literature on Akt and Pim signaling in cancer.
- Analysis of studies investigating the impact of Akt and Pim modulation on drug sensitivity.
- Examination of preclinical and clinical data on small molecule inhibitors.
Main Results:
- Akt and Pim activation promotes cancer cell survival and confers resistance to anti-cancer treatments.
- Inhibiting Akt and Pim pathways can sensitize cancer cells to cytotoxic drugs.
- Several small molecule inhibitors targeting these pathways are in development and clinical trials.
Conclusions:
- Akt and Pim signaling pathways are critical regulators of cancer cell survival and drug resistance.
- Targeting these pathways presents a viable strategy for improving cancer therapy.
- Future therapies will focus on selective induction of apoptosis and overcoming drug resistance via Akt and Pim inhibition.
More Related Videos
08:59Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down
Published on: December 11, 2017
09:56Promotion of Survival and Differentiation of Neural Stem Cells with Fibrin and Growth Factor Cocktails after Severe Spinal Cord Injury
Published on: July 27, 2014
Related Concept Videos
03:14Notch Signaling Pathway
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
02:33Hedgehog Signaling Pathway
01:19Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
01:41Non-Canonical Wnt Signaling Pathways
02:54Canonical Wnt Signaling Pathway
02:26NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The...