"There is evidence that the clonal evolution model may hold true for some cancers however, a growing body of scientific evidence supports a hierarchical model for the majority of solid tumors . For example, a recent study by Penny et al. looked at Gleason grade progression and found that even though PSA screening leads to a significant decrease of advanced prostate cancers, the Gleason grade did not follow this trend very closely, suggesting that in the vast majority of prostate cancers the most aggressive cell population arises early during cancer development  "
[Show abstract][Hide abstract] ABSTRACT: Since the first prospective identification of cancer stem cells in solid cancers the cancer stem cell hypothesis has reemerged as a research topic of increasing interest. It postulates that solid cancers are organized hierarchically with a small number of cancer stem cells driving tumor growth, repopulation after injury and metastasis. They give rise to differentiated progeny, which lack these features. The model predicts that for any therapy to provide cure, all cancer stem cells have to be eliminated while the survival of differentiated progeny is less critical. In this review we discuss recent reports challenging the idea of a unidirectional differentiation of cancer cells. These reports provide evidence supporting the idea that non-stem cancer cells exhibit a remarkable degree of plasticity that allows them to re-acquire cancer stem cell traits, especially in the context of radiation therapy. We summarize conditions under which differentiation is reversed and discuss the current knowledge of the underlying mechanisms.
Seminars in Cancer Biology 07/2014; DOI:10.1016/j.semcancer.2014.07.001 · 9.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Epstein histologic criteria (Gleason score <6, <2 cores positive, <50% of any core), established in 1994, have been widely used to select men for active surveillance. However, with the advent of targeted biopsy, which may be more accurate than conventional biopsy, we re-evaluated the likelihood of re-classification upon confirmatory re-biopsy using multi-parametric MRI-ultrasound fusion (mpMRI-US).
We identified 113 subjects enrolled in the UCLA active surveillance meeting Epstein Criteria who subsequently underwent confirmatory, targeted biopsy via mpMRI-US. Median age was 64 years, PSA 4.2 ng/ml and prostate volume 46.8 cc. Targets, or regions of interest on mpMRI, were graded by level of suspicion and were biopsied at 3 mm intervals along their longest axis (median 10.5 mm). Additionally, 12 systematic cores were obtained during confirmatory re-biopsy. Our reporting is consistent with START criteria.
Overall, confirmatory fusion biopsy resulted in re-classification for 41 men (36%), 26 (23%) due to Gleason grade >6, and 15 (13%) due to high volume Gleason 6 disease. When stratified by suspicion on mpMRI, the likelihood of reclassification was 24% to 29% for men with target grade 0 to 3, 45% for grade 4, and 100% for grade 5 (p=0.001). Men with grade 4 and 5 versus lower grade targets were >3 times (Odds Ratio 3.2, 95% Confidence Interval 1.4, 7.1, p=0.006) more likely to be reclassified.
Upon confirmatory re-biopsy using mpMRI-US, men with high-suspicion mpMRI targets were frequently reclassified (45%-100%). Criteria for active surveillance should be re-evaluated when mpMRI-guided prostate biopsy is employed.
The Journal of urology 02/2014; 192(2). DOI:10.1016/j.juro.2014.02.005 · 4.47 Impact Factor
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