The processes that control normal cell activity are complex and multi-level and mutations in any number of them can lead to cancer – the continual, unregulated proliferation of cells that grow, reproduce and eventually migrate throughout the body.
There are over 200 different types of known cancers, classified based on the type of cell from which they arise, falling into three main groups:
Further classification is based on the type of cell involved and the tissue of origin – for example erythroid leukemias are precursors of erythrocytes. The four most common cancers are breast, prostate, lung and colon, accounting for more than 50% of all cancer cases.
Bioline offers an excellent range of end-point and real-time PCR reagents and kits to support research into the genomics of cancer and cancer-related mutations. Usually a number of mutations are required before a cell exhibits cancerous properties, typically involving abnormalities in the mechanisms that control cell proliferation, differentiation and survival.
There are a number of ways through which cancer cells can bypass normal proliferative mechanisms including producing their own growth-factor ligands, stimulating neighbor cells to produce various growth factors, or by altering cell surfaces to become hyper-responsive to growth factors. Research in this area looks at a number of different aspects of cell-growth mechanisms, such as mutations that lead to disruptions in the negative feedback mechanisms that reduce proliferative signalling, or those that aid in the evasion of growth suppressors, as well as somatic mutations that activate downstream pathways involved in cell proliferation.
The ability to evade apoptotic processes is another hallmark of cancerous cells, increasing their lifespans and significantly contributing to tumor growth. Upstream regulators and downstream effector components contribute to the apoptotic machinery of the cell environment and consist of both extra- and intra-cellular signalling pathways. There are a number of ways through which tumor cells circumvent or limit apoptosis, such as increasing expression of anti-apoptotic regulators, downregulating proapoptotic factors, or through the total loss of tumor suppressor genes.
In addition, many malignant cells secrete proteases to digest the components of the extracellular matrix and enable invasion of adjacent tissue. Another hallmark of cancer cells is the ability to promote the formation of new blood vessels – angiogenesis – required to supply much needed oxygen and nutrients to the proliferating tumor. The activation of this “angiogenic switch” can be related to factors that either induce or oppose angiogenesis and most likely a number of countervailing factors. The ability to metastasize, that is to migrate or spread to another part of the body not directly connected with the original tumor, involves a complex invasion-metastasis cascade that is still being understood and includes mechanisms that both allow for physical dissemination from the primary tumor, as well as adaptation to the foreign tissue environment at the secondary destination.
Real-Time PCR Assay panels of a full range of miRNA targets associated with cancer-related processes are also available to assist researchers in identifying appropriate targets for further study and ISO 13485 manufactured reagents provide the required quality for developing assays for personalised medicine approaches.
Since the completion of the Human Genome Project and the continued progression of deep sequencing approaches for a range of tumors and cancer types, there has been much hope that identification of key oncogenes would become evident and once identified, ways in which to counter their activation could be devised. What has instead come to light is an unpredicted level of diversity both within and between cancers that have been sequenced thus far. Mutations in several hundred different genes have been identified as drivers of cancer and while data is still being gathered, no clear candidates for subsequent treatment development have emerged thus far, so research efforts continue.
Physiological or phenotypic variations can be observed in genetically identical cells that contain, for example, differences in DNA methylation or histone modifications, properties that alter the transcriptional potential of a cell. Epigenetic changes can occur as a result of environmental influences, they are heritable as well as reversible and epigenetic changes contribute to carcinogenesis, thus studies in cancer epigenetics are thriving and this area holds promise for the development of cancer treatment options.
It is difficult to dissociate the microenvironment from traditionally defined cancer cells, however data suggests that dysfunction within the microenvironment is linked to carcinogenesis, thus understanding the pathophysiology of the microenvironment is a path towards development of chemopreventive agents. Research in this area attempts to understand the dynamic and reciprocal interactions between tumor cells and the cells that orchestrate their growth, metastatic properties or drug resistance progression.
A wide range of biomarkers for cancer have been identified across the full spectrum of cellular processes involved in the disease and these biomarkers can be used to estimate risk towards developing disease, screen for active disease, determine disease prognoses, and both predict response to therapy and monitor therapeutic responses. There are many researchers committed to unravelling the immense complexity of biological and cellular information that has been collected thus far across the 200-odd diseases that are collectively known as cancer. Insights into this diversity and individual correlations within disease state form the foundation of biomarker development and subsequent personalized medicine. Today almost half of the cancer medicines and treatments in development are linked to small-molecules or novel biologic agents that have been identified as biomarkers for disease and this figure is only likely to increase as research continues in this area.
