Cancer Arrays and Assays

Cancer

Cancer is a genomic disease. Carcinogenesis or tumorigenesis is a result of genetic and epigenetic changes. There are more than a hundred distinct types of cancer. The most common types are breast, bladder, colon-rectal, endometrial, kidney (renal cell), leukemia, lung, melanoma, non-Hodgkin lymphoma, pancreatic, prostate, skin (non-melanoma), and thyroid cancer. For every type of cancer, there are six hallmarks: self-sufficiency in growth signals, resistance to growth inhibitory signals and anti-cancer therapy, evasion of programmed cell death, unlimited replication capability, sustained ability of angiogenesis, and invasion and metastasis. See details here.

Two main categories of genes are involved in carcinogenesis: oncogenes and tumor suppressor genes. Oncogenes are activated proto-oncogenes that are able to transform cells into malignant ones. Tumor suppressor genes can be inactivated through mutation, deletion, rearrangement, amplification, or methylation. Cancer cells can produce their own growth signals. Many oncogene products act by mimicking growth factors. Growth factor receptors such as HER2/neu, often having tyrosine kinase activities, are either overexpressed or mutated. In cancers, intracellular proteins that transduce growth signals are often overexpressed or activated by mutation, such as ras in MAPK signaling pathway. With these self-sufficient mechanisms, cancer cells can be totally growth-independent of their environment.

Many anti-proliferative signals are funneled through the tumor suppressor retinoblastoma protein (pRb). Disruption of pRb signaling is a good example of tumor suppression loss in cancer. The most commonly occurring loss of a pro-apoptotic regulator through mutation or deletion involves either the p53 or PTEN tumor suppressor genes. Cancer cells also use various strategies to avoid differentiation. Overexpression of the c-Myc is seen in many cancers and can impair differentiation and promote cell growth.

A telomere is a region of repetitive DNA at the end of a chromosome which protects the end of the chromosome from deterioration. Telomere shortening prevents genomic instability and development of cancer by limiting the number of cell divisions. Malignant cells bypassing this cell cycle arrest mechanism become immortalized by telomere extension mostly due to the activation of telomerase - the reverse transcriptase enzyme responsible for synthesis of telomeres. Telomere maintenance is therefore a key component of the capability for unlimited replication. The role of telomerase in immortalizing cells can be demonstrated directly by ectopic expression in normal cells, where it can convey the potential for unlimited replication to the normal cells.

Oxygen and nutrient supplied by the vasculature are crucial for continuing cancer growth. Vascular endothelial growth factor (VEGF) and acidic and basic fibroblast growth factors (FGF1/2) are examples of angiogenesis (the formation of new blood vessels) initiating signals. Cancer induces the angiogenesis by changing the balance of angiogenesis inducers and inhibitors.

Invasion and metastasis are involved in 90% of human cancer deaths. Several classes of proteins that tether cells to their surroundings are altered in metastatic cells. They include cell-to-matrix adhesion molecules such as integrins, cell-to-cell adhesion molecules such as E-cadherins, and proteases such as matrix metalloproteinases (MMPs).

Nearly every known signaling pathway can play a role in cancer. An important question is whether common signal transduction pathways are ubiquitously altered in all cancer types and some unique pathways are involved in different cancer types. Evidence suggests that the common signaling pathways are frequently activated in most tumor types. Since multiple pathways are dysfunctional in most cancers, and cancers accumulate new oncogenic mutations as they progress, the greatest and most durable therapeutic benefit will likely be achieved with combination of regimens that address several targets at a time.

Microarray technology allows scientists to detect the expression of tens of thousands of genes all at once, providing a molecular "fingerprint" or "signature" of a particular type of cancer. The amounts of data these experiments create, however, can be difficult to sift through and make sense of. With QIAGEN's much more focused PCR arrays, you can quickly spot the aberrant expression of cancer-related genes. These PCR arrays are Cancer PathwayFinder, Apoptosis, Cell Cycle, DNA Damage, Extracellular Matrix (ECM) and Adhesion Molecules, EMT, Tumor Metatstasis, VEGF Signaling, Angiogenesis, Breast Cancer and Estrogen Receptor Signaling, PI3K-Akt Signaling, TGF-beta / BMP Signaling, p53 Signaling, Wnt Signaling, MAPK Signaling, Protein Phosphatases, Cancer Drug Resistance and Metabolism PCR arrays, etc. Besides, QIAGEN also provides powerful epigenetic tools. Human Oncogenes and Tumor Suppressor Genes ChampionChIP PCR Array contains 96 pairs of qPCR primers targeting the 1-kb region downstream of the transcription start sites (TSS) of 84 important oncogenes and tumor suppressor genes plus 12 control regions. The results can provide great insight into which oncogenes and tumor suppressor genes are directly bound by your protein of interest. You can also quickly profile the methylation status of up to 96 tumor suppressor genes in your sample by using our Cancer Methylation PCR arrays.