Cancer can be defined as a disease in which a group of abnormal cells grow The foundation of modern cancer biology rests on a simple principle – virtually. BIOLOGY. We now understand a lot about cancer. We know that it results from a series of genetic changes having to do with cell division and growth control and. The Biology of Cancer. First Edition. Chapter The Rip-Tag model of islet cell tumor progression Metastatic cancer cells in bone marrow (Wright-Giemsa stain.
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Cancer arose with advent of multi-cellularity million years ago. Each cell gains the right to multiply independently. Must be mechanisms to tailor proliferation. A class of genetic diseases, in that aberration of key genetic and resultant molecular pathway are critical for carcinogenesis. Cancer is not a single disease, but. PDF | Michel-Saveur Maira did his PhD in molecular and cellular biology in the laboratory of Dr B Wasylyk (IGBMC, ULP, Strasbourg, France).
The ECM stores GFs in inactive forms, which are released by active matrix proteases and stimulate the growth of tumour cells in a paracrine manner. Stromal cells within the ECM may directly transmit oncogenic signals to tumour cells. Back to top Other genetic aspects of cancers Apart from the three major types of genes frequently altered in cancer, i. Back to top Genetic instability of tumour cells Genetic analysis of solid tumours revealed the presence of a high degree of genetic abnormalities, such as aneuploidy, chromosome translocations etc.
This is likely due to the lack of active p53 protein, and the ability of cancer cells to avoid cell death through apoptosis. Other mechanisms may also play a part here, e.
Chromosomal instability CIN is widespread in cancer cells from epithelial origin, but much rarer in haematopoietic tumours. Alteration of genetic mechanisms in cancer Three different alterations of genetic mechanisms often observed in cancer will be briefly explained below.
Loss of heterozygosity LOH : This describes a genetic phenomenon often seen with tumour suppressor genes in cancer. Since the human karyotype is diploid, mutation of one allele of a tumour suppressor gene is not sufficient to cause cancer.
In heterozygous individuals, the wildtype allele will provide for a functional phenotype. Genetic analyses of LOH helped to identify the chromosomal location of many tumour suppressor genes. Microsatellite instability MIN : This is a phenomenon often seen in colorectal cancer cells with defective DNA mismatch repair system, e. Microsatellites are regions of repetitive DNA sequences in the genome that are prone to shortening or extension if the mismatch repair enzymes are defective.
Genetic analysis of these regions can be used to identify such defects. DNA hyper- or hypomethylation: DNA methylation of gene promoter regions on CpG cytosine-phosphate-guanine sequences is an important epigenetic control mechanism to silence specific genes.
In cancer, DNA hypermethylation is often involved in the silencing of tumour suppressor genes. Conversely, DNA hypomethylation may contribute to the activation of oncogenes, although the former occurs much more commonly. Inherited predisposition to cancer Whilst cancer as such is not inherited, there are a wide range of rare familial syndromes that predispose affected family members to cancer development.
We mentioned above cancer predisposition syndromes that are based on mutations in DNA repair enzyme systems Table 4, in The importance of DNA repair systems. A by far larger number of familial cancer syndromes is based on mutations of tumour suppressor genes, of which a selection is shown in Table 2.
It is interesting to note that germ line mutations of activated oncogenes are normally not inherited. They may arise during gametogenesis, but the mutant alleles are typically dominant at the cellular level, which results in disturbance of normal embryonic development, and reduced viability of these embryos.
Fortunately, the inherited cancer predisposition syndromes listed in Tables 2 and 4 are extremely rare diseases, but they represent powerful illustrations for the importance of DNA repair and tumour suppressor genes for maintaining body homeostasis.
Principal applications of genetic testing in cancer As an increasing number of cancer-related genes or gene mutations is characterised, the potential of DNA and RNA expression testing for cancer-related applications is being explored. Principal applications include: Gene mutation screening in families with inherited cancer predisposition syndromes, which identifies at- risk individuals in such families and allows for decisions to be made about early disease monitoring, aggressive treatment regimens and prophylactic surgery e.
Gene expression microarray analysis can be used for classification of cancer subtypes, e. Other applications include the diagnosis of benign vs. Tumour cells may be recognised by the immune system through the expression of tumour-associated antigens, but the antigenicity varies considerably between different types of antigens.
In order to avoid an attack by the immune system, tumour cells use a range of strategies, such as suppression of expression of tumour-associated antigens or of MHC class 1 molecules, or even counterattack against immune cells.
Research into immunotherapy of cancers aims to devise novel strategies to support the anti-cancer immune response; principal approaches include: Antigen-independent cytokine therapy e. Herceptin, Rituxan. Novel approaches arising from cancer cell biology The progress in our knowledge about gene mutations frequently occurring in cancers, combined with the development of modern molecular biology methods has led to both new diagnostic tools see Principal applications of genetic testing in cancer and new treatment modalities that have shown some success in the management of selected types of cancers.
The knowledge about cancer—associated genes and their role in cellular growth signalling pathways has led to the development of a considerable number of anti-cancer drugs targeting such signalling pathways: 1 monoclonal antibodies that target the extracellular domains of growth factor receptors and 2 small-molecule inhibitors, targeting either receptor tyrosine kinases or other components of growth signalling pathways, such as Ras, b-Raf or mTOR Figure. Two examples of such successful anti-cancer agents are the monoclonal antibody Herceptin for the treatment of a specific subtype of breast cancer, and the small-molecule inhibitor Gleevec targeting the fusion protein Bcr-abl, a mutant tyrosine kinase, involved in the development of chronic myeloic leukaemia CML.
A third group of potential drug targets are some anti-apoptotic proteins that are frequently overexpressed in cancer cells.
Figure 6. Targets of novel anti-cancer drugs in cellular growth signalling pathways. The cell membrane is indicated in light grey, red diamonds represent growth factors, green shows the growth factor receptor with the intracellular tyrosine kinase domain Tk indicated by the red circle. Dotted black arrows point to cell biological outcomes of these pathways. Groups of novel anticancer drugs and their targets are shown in red.
The biology of cancer. Additional capabilities crucial to cancer phenotypes that are not shown here include defects in DNA repair mechanisms and signalling interactions of the tumour microenvironment. Hallmarks of cancer: the next generation. Cell,  Self-sufficiency in growth signals: Tumours have the capacity to proliferate without external stimuli, usually as a consequence of oncogene activation.
CSA Address: Updated April, The evolving technologies in molecular biology, imaging, and rational drug design and screening have lead to rapid expansion of new strategies for prevention, detection and treatment of human malignancies. The goal of the Cancer Biology Track is to educate the next generation of cancer researchers to meet the growing demands for scientists trained in multiple facets of cancer biology. The curriculum stresses both basic and translational research to provide the broad background in oncology needed for today's research.
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