In biology we can observe many examples where a continuous/permanent expression/contact of a signal to the target cells results to the “non-response” or the resistance of the target cells to this signal.
We can provide as examples the resistance to the antibiotics (antibiotic resistance & antimicrobial resistance); the resistance to the chemotherapies – like the one seen in the case of Acute Promyelocytic Leukemia (APL) and the cell resistance to the retinoic acid drug. Cell resistance to RA blocks cell remission.
As in the case of chemotherapies, antimicrobial resistance is resistance of a microorganism to an antimicrobial drug that was originally effective for treatment of infections caused by it.
Antibiotic resistance refers specifically to the resistance to antibiotics that occurs in common bacteria that cause infections. Antimicrobial resistance is a broader term, encompassing resistance to drugs to treat infections caused by other microbes as well, such as parasites (e.g. malaria), viruses (e.g. HIV) and fungi (e.g. Candida).
Whereas, the Antibiotic and Antimicrobial resistance seem to relate to the properties of the microorganisms, the Chemotherapy resistance relates to the properties of the target cells.
Do you think that both resistances to the target signal (drug) might have a common initial early post-genomic cause in an eukaryotic environment - or both reflect late genomic modifications of the target cells (either eukaryotic cells or microorganism) ?
PS. Do you think that cell resistance might have a similarity with the concept illustrated in the phase of the 1st President of kenya – Jomo Kenyata 1891-1978: “When the Missionaries arrived, the Africans had the Land and the Missionaries had the Bible. They taught us how to pray with our eyes closed. When we opened them, they had the land and we had the Bible.” Jomo Kenyata
Intracellular signaling pathways encompass highly interconnected networks and if resistance occurs in one direction, it will be eventually bypassed by other side way pathways and I think that profiling on the level of proteomics & metabolomics would unravel many of the mechanisms of drug resistance.
Dear Ahmed,
Certainly, proteomics and metabolomics and genetics would help to understand cell signaling and in that sense further understand drug resistance mechanisms and more. The question is if a common mechanism could unify apparently distinct signaling pathways such as the resistance to antibiotics and the resistance to chemotherapies.
I prefer to advance science with a scientific/philosophical model then establish a hypothesis and a research working plan and then the scientific evaluation and applications. The classical method exemplified by many with the statement ‘knock-out a gene and identify a function” is not a scientific approach. Biology is an exact science then we have to find mathematical and physical/philosophical laws that could help us to understand and explain cell signaling. Drug resistance is part of this scientific concern.
Dear Vassilis,
I don't agree completely with your opinion that the classical method exemplified by many with the statement ‘knock-out a gene and identify a function” is not a scientific approach. I think that method added much information about the pathogenesis of many diseases, but in cancer, in particular, the subject is so complex.
Caner stem cell & cancer evolution models are the best examples that describe how cancer cell phenotypic changes occur by acquisition of sequential mutations, that render just to specify the cancer stem cell which should be targeted is so difficult.
The problem lies in the lack of knowledge of the target, not just resistance occurring due to dealing with the target.
Dear Vassilis,
I recommend
http://www.tandfonline.com/doi/pdf/10.4161/cc.24479
http://onlinelibrary.wiley.com/doi/10.1002/stem.2099/full
Dear Ahmet,
There are 4 major sciences; Philosophy, Mathematics, Physics and Biology. The art of experimental mutagenesis is an experimental/technical approach. Of course you are welcome to do not agree.
Best, Vassilis
I agree with you that there are 4 major sciences; Philosophy, Mathematics, Physics and Biology.
And I also completely agree that biology is an exact science then we have to find mathematical and physical/philosophical laws that could help us to understand and explain cell signaling. Drug resistance is part of this scientific concern.
I'm not entirely convinced with the geno-centric approach 'experimental mutagenesis' as the sole way for conducting research
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