[gdpawel]

According to some researchers, cancer is about the properties of evolutionary populations of cells. They feel that three conditions must be satisfied for effective control of cancer or finding its cure: comprehensiveness, specificity and knowability.

Comprehensivenss refers to the ability to kill or inactivate all malignant cells in the patient (if one malignant cell escapes, it could multiply and cause progressive disease). Specificity refers to the ability to target cancer cells without harming normal cells or causing toxicity to the patient. Knowability refers to the need to target properties of cancer that can be known, or accurately predicted.

Targeting genetic alterations can provide a basis for specificity but not comprehensiveness and knowability. The diverse, evolutionary nature of cancer implies that the required target for the consistent and specific cure or control of cancer is all the sets of malignant cells that could evolve. An approach targeting a lesser set will fail. It cannot satisfy the requirements for targeting an evolutionary population of malignant cells.

The set of all malignant cells that could evolve must apply to all pathways of tumor cell evolution and all combinations of genetic and epigenetic alterations. It must be independent of any particular pathway of tumor cell evolution. The normal cellular machinery that potentially can carry out malignant behavior is encoded within the normal human genome, essentially the same for all types of cancer, and reflected in normal processes such as wound healing.

Finding mutations in kinase genes is neither surprising nor really good news. If you're trying to figure out how many combinations of these mutations one could have, and then consider that mutations are only the beginning because it depends on the factors which regulate those genes, and how much the genes are expressed or repressed, and how all those things interact with all the other things which are going on, it is going to be a major challenge if you want to build a model of cancer cells from the bottom up.

Without cell culture, gene therapy would be beyond imagination. Tissue culture methods have made gene therapy possible. The ability to transfect cultured cells with DNA gene sequences has allowed scientists to assign functions to different genes and understand the mechanisms that activate or redress their function. The interaction between cell biology and genetics gave birth to molecular biology.

Cell culture assays with cell-death endpoints allows the identification of clinically relevant gene expression patterns which correlate with clinical drug resistance and sensitivity for different drugs in specific diseases. There is no single gene whose expression accurately predicts therapy outcome, emphasizing that cancer is a complex disease and needs to be attacked on many fronts.

Cell culture assays using the whole cell profiling method assess the activity of a drug upon combined effect of all cellular processes, using combined metabolic and morphologic endpoints. Other tests that identify DNA or RNA sequences or expression of individual proteins often examine only one component of a much larger, interactive process. Drug resistance and sensitivity is multifactorial, and the one advantage of whole cell profiling is that it can show this at the cell population level, measuring the interaction of the entire genome.

Sources:

A. Glazier et al, Cure: Scientific, Social and Organizational Requirements for the Specific Cure of Cancer