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.
Complete Array List
