1-As we continue our exploration of signaling pathways in cancer, one important class of players (not discussed in detail in this unit) are MMPs (matrix metallopeptidases). These enzymes are involved in the breakdown of the extracellular matrix, and play important roles in embryogenesis, reproduction, tissue remodeling, and cancer development.

Researchers at MIT have developed a test to detect synthetic reporters that are cleaved by MMPs at disease sites with the aid of nanoparticle technology. The cleaved reporters are then filtered through the kidneys and can be detected in the urine. So far, this assay has been successfully tested in mice.

Thoughts on this? Breakthrough in cancer detection or too much potential for false positives?

For this question need your thought and concerns or if you have comments with referenced.

2- In colorectal cancer the cells of the colon become abnormal are proliferate uncontrollably. In the U.S this type of cancer is the second highest cause of cancer-related deaths after lung cancer. Because of this very poor prognosis of this type of cancer, developing a biomarker fpr predictive, early diagnosis and therapeutic reasons would be very beneficial. There is actually an urgent need presently for biomarkers for colorectal cancer to accurately identify patients at-risk for disease recurrence and dissemination, along with those that fail to respond to systemic therapy. Extensive CRC research over the last decade has suggested promising biomarkers. These include epidermal growth factor receptor (EGFR), BRAF, tumor MSI-H expression (defects in DNA mismatch repair, MSI phenotype), 18q AI expression, p53 expression and KRAS mutation.

The addition of cetuximab to standard cytotoxic chemotherapy has shown a progression-free survival benefit but no benefit in overall survival. On further analysis, this benefit was only found in the Kirsten-RAS (KRAS) wild-type patients. This is because a mutation in the KRAS gene leads to constitutive activation of the EGFR signaling pathway, thereby eliminating any effects of upstream EGFR blockade. This finding has led to the selection of patients for EGFR blockade therapy based on KRAS status, with cetuximab only offered to those patients with no KRAS mutation in the primary tumor.

KRAS status as a biomarker would then be helpful in selecting treatment options for patients with colorectal cancer. However KRAS mutation is not specific to colorectal cancer, it is also seen in breast cancer, and prostate cancer and they are several sub-types of this mutation. Nevertheless, in my opinion biomarkers are of great value in predicting risk of cancer, and evaluating prognosis. Despite the low specificity that are sometimes observed in biomarker testing, they can still be beneficial especially as a first-line screening method. This allows for subjection to more invasive methods only if indicated necessary by the presence of these biomarkers. CEA, CA125, and even PSA are some of the well-developed cancer markers that playing a very helpful role in early detection of cancer as well prognosis evaluation. Hopefully a biomarker can also be adequately developed for colorectal cancer.

Weingburg R. The Biology of Cancer.May 2013

Langan et al Colorectal Cancer Biomarkers and the Potential Role of Cancer Stem Cells. J Cancer 2013; 4(3):241-250. doi:10.7150/jca.5832.