Cancer myths
Since the time of Virchow, the first person to sucessfully apply the microscope to human pathology, cancers have been calssified ccording to their "site of origin." Virchow lived in a time when the details of anatomy were being discovered. With the microscope the pathologists ( histologist) could identify patterns of cells that (seemed) characteristic of particular tissues and/or organs. Amazingly, there was often a correlation between the cell patterns and the gross anatomy - collections of cells that looked like they came from the kidney ofen correlated with the identification of a mass in the kidney! It seems true that cancer cells keep some of the characteristics of their origins. This statement has various levels of meaning. The ususal action ascribed to it is that cancers are catagorized, and thus treated, accoding to their established or presumed cell of origin.
However, we have a deepening understanding of cells that goes far beyond their appearance. Identical appearing "lymphocytes" are standardly differentiated by immuno chemical means and the results generates a varation in treatment. The idea of cell of origin is expanded to include the catagorization of tumors, on the basis of immunocytochemical analyses, to theoretical sites of origin.
The implicit meaning of the idea of cells of origin is that tumors retain characterisitice of their origins that inform their behavior and susceptibilities. I think that there is limited truth to this. THis idea has been a way to generate ideas about potential treatments for cancers. THus, fluorouracil, which causes diarrhea, might be a good tretment for lung cancer; DDT, which causes adrenal failure could treat adrenal cancer, etc. This was not a terrible strategy given the paucity of active agents and the generally low expectations.
The tissue of origin might also predict a general resistance to chemothehrapy and/or other therapies. Thus kidney cells that function to excrete poisons are exprected to be resistant to chemotherapy. The same argument pertains to colon cells or bladder cells. The truth value of this agrgument is not clear to me. Myths?
Along comes molecular biology. There are many components to molecular biology. DNA expression in all its twists and turns ( enhancers, splice choices, siRNA, etc), signal transduction, proteasomes, angiogensis, etc.. each is a model for cancer and each contains some value, none is the whole answer and probably not even their overlap constitutes a complete enough answer to apply across all cancers.
The array of expressed genes is probably the closest we currently come to a functional description of the situation in cancer cells. But the technique is not good. It generates a list of genes that are either overexpressed ot underexpressed in cancers. There is an admixture of statistics that are not clearly appropriate, arbitrary cutoff levels that define over or underexpression, ignorance of the interaction among the genes, etc. But even if all of these issues were sorted out, I am not convinced that the answer would be very useful.
The Oncotype is a commercialization of (an early form) of this technology. It is living its oncology life: Initial excitement, statistical significance in a few clinical trials, commercialization, exorbitant prices and profits, flaws emerge, junked.
Since the time of Virchow, the first person to sucessfully apply the microscope to human pathology, cancers have been calssified ccording to their "site of origin." Virchow lived in a time when the details of anatomy were being discovered. With the microscope the pathologists ( histologist) could identify patterns of cells that (seemed) characteristic of particular tissues and/or organs. Amazingly, there was often a correlation between the cell patterns and the gross anatomy - collections of cells that looked like they came from the kidney ofen correlated with the identification of a mass in the kidney! It seems true that cancer cells keep some of the characteristics of their origins. This statement has various levels of meaning. The ususal action ascribed to it is that cancers are catagorized, and thus treated, accoding to their established or presumed cell of origin.
However, we have a deepening understanding of cells that goes far beyond their appearance. Identical appearing "lymphocytes" are standardly differentiated by immuno chemical means and the results generates a varation in treatment. The idea of cell of origin is expanded to include the catagorization of tumors, on the basis of immunocytochemical analyses, to theoretical sites of origin.
The implicit meaning of the idea of cells of origin is that tumors retain characterisitice of their origins that inform their behavior and susceptibilities. I think that there is limited truth to this. THis idea has been a way to generate ideas about potential treatments for cancers. THus, fluorouracil, which causes diarrhea, might be a good tretment for lung cancer; DDT, which causes adrenal failure could treat adrenal cancer, etc. This was not a terrible strategy given the paucity of active agents and the generally low expectations.
The tissue of origin might also predict a general resistance to chemothehrapy and/or other therapies. Thus kidney cells that function to excrete poisons are exprected to be resistant to chemotherapy. The same argument pertains to colon cells or bladder cells. The truth value of this agrgument is not clear to me. Myths?
Along comes molecular biology. There are many components to molecular biology. DNA expression in all its twists and turns ( enhancers, splice choices, siRNA, etc), signal transduction, proteasomes, angiogensis, etc.. each is a model for cancer and each contains some value, none is the whole answer and probably not even their overlap constitutes a complete enough answer to apply across all cancers.
The array of expressed genes is probably the closest we currently come to a functional description of the situation in cancer cells. But the technique is not good. It generates a list of genes that are either overexpressed ot underexpressed in cancers. There is an admixture of statistics that are not clearly appropriate, arbitrary cutoff levels that define over or underexpression, ignorance of the interaction among the genes, etc. But even if all of these issues were sorted out, I am not convinced that the answer would be very useful.
The Oncotype is a commercialization of (an early form) of this technology. It is living its oncology life: Initial excitement, statistical significance in a few clinical trials, commercialization, exorbitant prices and profits, flaws emerge, junked.
Labels: Cancer myths
posted by Sheldon Goldberg at 4:41 PM
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