Cancer Lecture Note

Cancer, The term cancer applies to a group of diseases in which cells grow abnormally. • A mass of tissue formed as a result of abnormal excessive, uncoordinated, autonomous and purposeless proliferation of cells is called tumor. ▪ Tumors may be ‘benign’ or “malignant” ▪ The term used for all malignant tumors is cancer. • Cancers are classified according to the tissue and cell types from which they arise, e.g. • Carcinomas: Cancer arises from epithelial tissues • Sarcomas: Cancer arises from mesenchymal tissues • Leukemia: Cancer of blood forming organs • Lymphoma: Cancer of lymph node • Hepatomas: Carcinoma of hepatocytes. CHARACTERISTICS OF CANCER CELLS Cancer cells are characterized by certain main properties 1. They proliferate rapidly 2. Show diminished growth control 3. Show loss of contact inhibition. Malignant tumors show faster rate of growth due to loss of contact inhibition and form multilayers instead of a monolayer. 4. They invade local tissues and spread, or metastasize, to other parts of the body. 5. They are self-sufficient in growth signals and are insensitive to antigrowth signals 6. They stimulate local angiogenesis 7. They are often able to evade (escape) apoptosis Major characteristics of cancer cells. MOLECULAR BASIS OF CANCER (CARCINOGENESIS) ▪ Carcinogenesis means mechanism of induction of tumors (cancer). ▪ Agents which can induce cancer are called carcinogens. CARCINOGENS Agents which can induce cancer are called carcinogens. Carcinogens are a variety of external agents which are divided into three groups: 1.Chemicals 2. Radiant energy 3. Certain oncogene viruses Chemical Carcinogens ▪ A wide variety of chemical compounds are carcinogenic ▪ Depending upon the mode of action of carcinogenic chemicals, they are divided into two groups: 1. Initiators of carcinogenesis 2. Promoters of carcinogenesis. Initiators of Carcinogenesis ▪ These are the chemical carcinogens which can initiate the process of abnormal new growth of cells. ▪ Initiation is the first stage in carcinogenesis. Examples : • Aromatic hydrocarbons : Tobacco smoke, industrial and atmospheric pollutants. • Aromatic amines, e.g. Benzidine, β-naphthylamine. • Naturally occurring products, e.g. Aflatoxin B Promoters of carcinogenesis ▪ Certain chemical substances are not carcinogenic but they help the initiated cell to proliferate further are called promoters of carcinogenesis. ▪ For example, phenols, phenobarbital, artificial sweetners like saccharine and cyclamates. Action of chemical carcinogens ▪ Direct or indirect acting carcinogens are usually electrophiles, i.e. they are deficient in electrons (free radicals). ▪ These free radical carcinogens can covalently bind to purines, pyrimidines and phosphodiester bonds of DNA causing unrepairable damage. ▪ These unrepaired damage generate mutations in DNA and mutation in DNA may lead to cancer. Action of chemical carcinogens ▪ Direct or indirect acting carcinogens are usually electrophiles, i.e. they are deficient in electrons (free radicals). ▪ These free radical carcinogens can covalently bind to purines, pyrimidines and phosphodiester bonds of DNA causing unrepairable damage. ▪ These unrepaired damage generate mutations in DNA and mutation in DNA may lead to cancer. Action of chemical carcinogens. Radiant energy ▪ Radiant energy can be carcinogenic. ▪ Ultraviolet rays and ionizing radiation, i.e. X-rays, α-, β-, and γ-rays are mutagenic and carcinogenic. ▪ These rays damage DNA which is the basic mechanism of carcinogenicity with radiant energy. Oncogenic viruses ▪ Both DNA and RNA viruses have been identified as being able to cause cancer in humans. ▪ The RNA viruses use RNA as the genome. RNA oncogenic viruses are retroviruses, i.e. they contain the enzyme reverse transcriptase. ▪ All retroviruses are not oncogenic. Mechanism of Viral Oncogenesis ▪ The genetic material of viruses is incorporated into the genome of the host cell. ▪ The DNA virus infects the host cell. Then DNA virus binds tightly to host cell DNA and causes alterations in gene expression and thus causes cell transformation by altering the types of protein made in cell. ▪ Viral oncoproteins bind to tumor suppressors and inactivate them. ▪ DNA viruses act by down regulating the function of tumor suppressor genes P53 and RB and their protein products. ▪ The RNA viruses use RNA as the genome. ▪ The RNA gets copied by reverse transcriptase to produce single strand of viral DNA. ▪ Single strand of viral DNA is then copied to form another strand of complementary DNA, resulting in double stranded viral DNA called the provirus. ▪ The provirus is then integrated into the DNA of the host cell DNA and results in various activities such as: − Deregulation of the cell cycle − Inhibition of apoptosis − Abnormalities of cell signalling pathways ONCOGENES AND PROTO-ONCOGENES ▪ An oncogene is an altered gene derived by “activation” of normal cellular proto-oncogenes. ▪ Oncogenes encode a wide variety of proteins that accelerate cell growth or cell division. ▪ Cellular proto-oncogenes code for a number of proteins, e.g. growth factors, receptors, transcription factors and other proteins involved in cell growth. ▪ When proto-oncogenes get mutated they become oncogenes ▪ When oncogenes are expressed, they produce mutated versions of: − Growth factors − Receptors for growth factors − Proteins involved in signaling gene expression in the nucleus. TUMOR SUPPRESSOR GENES ▪ A tumor suppressor gene produces a protein product that normally suppresses cell growth or cell division. ▪ It regulates cell cycle and apoptosis. ▪ These tumor suppressor genes, sometimes called recessive oncogenes or anti-oncogenes. ▪ When such a gene is altered by mutation, the inhibitory effect of its product is lost or diminished, leading to increased cell growth or cell division. ▪ Inactivation by mutation of tumor suppressor gene removes certain mechanisms of growth control and can cause some types of tumor. ▪ Two of the most widely studied tumor suppressor genes are retinoblastoma (RB) gene and P53gene. TUMOR BIOMARKERS ▪ Many cancers are associated with abnormal production of enzymes, proteins, and hormones that can be measured in plasma or serum. ▪ These molecules are known as tumor biomarkers, which may suggest the presence of a type of cancer.. Clinical applications of tumor biomarkers Tumor biomarkers can be used in a number of ways including: ▪ Screening in general population ▪ Differential diagnosis in symptomatic individuals ▪ Clinical staging of cancer ▪ Prognosis of disease ▪ Evaluation of success of treatment ▪ Detection of recurrence of cancer ▪ Monitoring of response to therapy