There is seemingly no shortage of markers for cancer cells in vitro. Every week brings a new antigen, genotype, morphology, or molecule for identifying some particular cancer cell line or behavior. The tools available for identifying additional markers are also improving.
High-throughput assays such as next-generation sequencing, cDNA and protein microarrays, and ELISA/purification-assisted mass spectrometry provide a better look into the molecular world of cancer biology. At the same time, computing resources permit analysis across more datasets (different cell lines) and data types (proteins, mRNA, epigenetic modifications, and genomes), generating even more hits.
Cancer Then and Now
While the equipment and procedures for identifying these hits was improving, so too did the understanding of cancer behavior. The immense complexity and diversity of cancer was highlighted as more genotypes and phenotypes were found in patient cells.
Tumors once thought to be monocultures of malignant cells have actually turned out to be micro-ecosystems consisting of several populations of cells including cancer stem cells. The concept of the tumor microenvironment came to the forefront, and models of metastasis changed as nonmetastatic populations of circulating tumor cells were found.
This new understanding of cancer is immensely helpful in further research, but it does not bode well for individual use of biomarkers. The complicated behavior of so-called cancerous cells has forced questions of how to precisely define “cancerous” for the purposes of screening, diagnosis, and treatment.
In an editorial in the May 5, 2010, edition of the Journal of the National Cancer Institute, Drs. Laura Esserman and Ian Thompson discuss the over-diagnosis of cancer: they suggest that, considering approximately 75% of biopsies produce negative results, more focus should be given to distinguishing aggressive cancers from indolent ones rather than widespread nonspecific screening.
One much-maligned biomarker serves as an excellent example: prostate-specific antigen (PSA). Both the American Cancer Society and the NCI admit that the harm of overtreatment and cost of doing PSA screening outweigh the benefits of the test.