Question ID: Oct 9-3
Submitted by: October 9, 2010 Provocative Questions Workshop - Submitted to the website
December 17, 2010
Are there definable properties of non-malignant lesions that predict the likelihood of progression to invasive disease?
Background: Currently, the detection of non-malignant (presumptive pre-malignant) lesions, such as so-called “in situ carcinomas” of the prostate gland or breast, are often treated vigorously because of the possibility that they represent pathologies that are likely to adopt aggressive behaviors with time. It is difficult to reverse this pattern of care without knowing whether it is possible to judge its malignant potential from the genetic, biochemical, or cellular features of the lesion.
Feasibility: The advent of technologies that permit determination of genotypes and phenotypes of very small collections of cells may now reveal whether the malignant properties are conferred stochastically or whether early lesions differ in definable and reproducible ways with respect to the likelihood of malignant conversion.
Implications of success: Knowing whether early lesions can be categorized with high levels of confidence into groups with low, intermediate, or high predictive value for progression to invasive cancer would strongly influence both the search for early lesions in various cancer-prone tissues and the therapeutic decisions that are already being made. Insight into the biological basis for this stratification would be an important advance with possible relevance to analogous lesions of several tissues.
Average Score: 5.0
 (1 evaluation)Provocativeness - 5.0
Novelty - 4.0
Public Health Significance - 5.0
Feasibility - 5.0
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Comments
Submitted By Jerry Shay
The problem is having genetically tractable cell models to study the early events in cancer progression.
We barely know how to culture malignant human tumors in vitro. Most scientists only work with tumor cell lines that have been adapted to cell culture conditions for decades (we all like to work with cells that grow rapidly). However, if we are to make progress in understanding the initiation and early events leading to genetic and chromosome instability, it would help to learn how to grow human cells from early precancerous lesions. The days of Dulbecco, Ham etc are past but perhaps putting some resources into learning about culturing human normal epithelial cells (and avoiding culture shock) as well as precancerous lesions could help open up some new avenues in combination with the new generation of DNA sequencing.
Submitted By David Chia
Thia highly answerable question will have majore impact on therapeutic decisions.
