Cancer --an Overview

1. Cancer --an Overview • Cell Division • Hormones and Cancer • Malignant Transformation • Angiogenesis and Metastasis • Growth Factors and Oncogenes • Chemotherapeutic Drugs and Resistance • Clinical Oncology and Pathology • Tumor Virology and Immunology • Cancer Prevention and Control http://www.cancergenetics.org/

2. -Normal cell differentiation is altered in cancer cells.-Cancer cells have lost ability to control cell proliferation.-Cancer cells evolve clonally from a single cell as the result of specific mutations that affect basic cell processes.-It takes a sequence of mutational events, not just one, to lead to cancer.-Cancer cells have high levels of genomic instability(rearrangements in chromosomes).-Familial predisopsitions to cancer are the result of inheriting one of the mutations leading to cancer. http://www.fhcrc.org/education/courses/cancer_course/basic/abnormal.html

3. Cancer begins with a mutation in a single cell. People with hereditary cancer already have the first mutation.

4. Deletions are common in cancerous cells. http://nitro.biosci.arizona.edu/courses/EEB320/Lecture18/Lecture18.html

6. Examples of Oncogenes • erb-B codes for a receptor for epidermal growth factor; involved in glioblastoma, a brain cancer, and breast cancer • erb-B2 also called HER-2 or neu; involved in breast, ovarian, and salivary gland cancers • Ki-ras codes for a protein that relays a stimulatory signal; involved in lung, ovarian, colon, and pancreatic cancers • N-ras involved in leukemias • c-Myc, N-myc, L-myc all genes for transcription factors that activate growth promoting genes; involved in leukemias, breast, stomach, and lung cancers (c-Myc, L-myc); neuroblastoma (N-myc) • Bcl-1 codes for cyclin D1, a component of the cell cycle clock; involved in breast, head and neck cancers

7. The cell's progress from normal to malignant to metastatic follows a series of distinct steps, each controlled by a different gene or set of genes.

8. Growth Factors and Cancer • Epidermal Growth Factor (EGF) • Platelet-derived Growth Factor (PDGF) • Fibroblast Growth Factor (FGF) • Transforming Growth Factors Insulin-like Growth Factors (IGF1 and IGF2) • Nerve Growth Factors • Interleukins - Colony Stimulating Factors (CSF1, CSF2, Multi-CSF)

9. Tumor Suppressor Genes • Tumor Suppressor Genes, like other genes, are present in two copies per cell. • When one copy is "knocked out", cell growth is still normal, relying on the surviving gene copy. • Only when this second copy is also lost does abnormal proliferation take off.

11. Examples of Tumor Supressor Genes DPC-4 involved in pancreatic cancer; participates in a cytoplasmic pathway that inhibits cell division NF-1 involved in neurofibromas of the nervous system and myeloid leukemia; codes for a protein that inhibits Ras, a cytoplasmic inhibitory protein NF-2 involved in cancers of the nervous system; codes for a nuclear protein RB involved in retinoblastoma as well as bone, bladder, small cell lung, and breast cancers; codes of the pRB protein, a nuclear protein that is a major brake in the cell cycle p53 involved in a wide range of tumors; inactive or lost in more than 50% of cancerous cells; codes for the cytoplasmic p53 protein that regulates cell division and can induce cells to kill themselves (apoptosis); inheritance of p53 mutations through the germ line is also associated with the Li-Fraumeni cancer syndrome WT1 involved in Wilms tumor of the kidneys BRCA1 involved in breast and ovarian cancer BRCA2 involved in breast cancer

12. Mutations in DNA repair genes lead to an increase in the frequency of other mutations. Mutations in DNA helicase, an enzyme involved in maintaining DNA integrity. ----> Bloom Syndrome

13. Molecular Aspects of the Immune Response in Cancer