Harris Lecture 12 notes (1 per page)

Harris Lecture 12 notes (1 per page) - General cancer...

Info iconThis preview shows page 1. Sign up to view the full content.

View Full Document Right Arrow Icon
This is the end of the preview. Sign up to access the rest of the document.

Unformatted text preview: General cancer statistics for 2011 “Based on current incidence rates, 40-45% of Canadians will develop cancer during their lifetimes.” “On the basis of current mortality rates, approximately 1 out of every 4 Canadians, will die from cancer.” www.cancer.ca/statistics 1 1 To combat cancer we must understand what leads to cancer at the level of cells and molecules. Cancer progression occurs because of defects in the molecular machinery and regulatory mechanisms that normally control cell shapes, functions, interactions and numbers. 2 2 Molecular machinery and pathways linked to cancer 3 3 The basic biology of Cancer 14 10 cells in the hum an body There are > Billions of cells likely experience mutations every day by ap op tos is BUT, the body normally destroys aberrant cells on e of th es e ce Cancer develops from > gaining a mutation that allows it to survive and divide forming a tumour 4 4 Cancer develops from one cell that divides to form a tumour Evidence for the clonal origin of a tumour One of the two X chromosomes is inactivated in female cells (for dosage compensation) Every normal tissue of a woman’s body contains a mixture of cells with different X chromosomes inactivated All cells in a tumour have the same X chromosome inactivated… …thus the tumour is derived from single founder cell (otherwise it would be a mix like the surrounding tissue) 5 5 Cancer develops from one cell that divides to form a tumour With unconstrained growth a single cell can form a deadly tumour in less than 40 cell doublings > exponential growth can be surgically removed 6 6 Categorizing cancers by tissue type Tumour (neoplasm): > uncontrolled growing mass of abnormal cells Carcinoma: Epithelial cell cancers Sarcoma: Connective tissue or muscle cell cancers Leukemia: Blood cell cancers 7 7 Categorizing tumours by stage barrier between one organ and another Benign tumor: Growing mass is self-contained as a “single” tumor Malignant tumor (cancer): Aggressive tumor that has broken free and > invaded surrounding tissue 8 8 Categorizing tumours by stage still contained within the basal lamina cross through the extracellular space and go into the blood stream Metastatic tumour: Cancer invading other tissues 9 - usually via the blood stream or lymphatic vessels 9 Cancerous cells have disrupted DNA Karyotype of a cancer sample with many chromosomal abnormalities Karyotype of a tissue sample with a normal complement of chromosomes massive rearrangement in the genome! 10 10 What causes the mutations leading to cancer? What genes are mutated? How do the mutated genes promote cancer progression? 11 11 What causes the mutations leading to cancer? UV light, X-rays, viruses Chemical mutagens Example: not dangerous looking like a base, G cannot bind to C in the body, it's converted into a 2nd form-->dangerous 12 12 What causes the mutations leading to cancer? Chemical mutagens Testing: > The Ames Test not testing for cancer does this chemical cause a mutation? Their enzyme for making his is broken See if the mutagen can change it back. many other cells growing very difficult to look for a broken gene The liver extract supplies enzymes from human body to convert potential mutagen to be dangerous each colony comes from a single cell that is mutated 13 millions of individuals so we can pick up the event 13 What causes the mutations leading to cancer? What genes are mutated? How do the mutated genes promote cancer progression? 14 14 Cancer genes • Oncogenes: – Cancer arises from a > gain of function – The normal form of the gene is called a protooncogene (e.g. Ras, Myc) • Tumor suppressor genes: – Cancer arises from a > loss of function (e.g. p53, Rb) • Both types of mutation aberrantly enhance cell proliferation and survival 15 15 Oncogene mutations are dominant Tumour supressor gene mutations are recessive 16 16 Oncogene mutations are dominant Tumour supressor gene mutations are recessive 17 17 How are gain-of-function oncogenes produced? same amount, but hyperactive increase copies myc is put downstream?! a fusion protein that is hyper 18 18 How are oncogenes produced? e.g. the Philadelphia chromosome is a kinase inhibitory region is replaced 19 Bcr-Abl is an oncogene that causes chronic myelogenous leukemia 19 How are tumour supressor genes produced? Can be any inactivating mutational event (point mutation, deletion, etc.) But this event alone does not cause cancer because the other copy of the gene is still active 20 20 How can cells acquire mutations in both copies of a tumour supressor gene? 21 21 How can cells acquire mutations in both copies of a tumour supressor gene? 22 22 What causes the mutations leading to cancer? What genes are mutated? How do the mutated genes promote cancer progression? 23 23 How do mutations cause cancer? • Abnormal cell cycle - Leads to more cells in the tumour - Missed checkpoints permit further e.g. Myc mutations chromosomal aberrations 24 24 How do mutations cause cancer? • Abnormal cell cycle - Leads to more cells in the tumour - Missed checkpoints permit further chromosomal aberrations • Abnormal cell death - Loss of control of cell number - Apoptosis normally kills e.g. p53 mutations dangerous cells 25 25 How do mutations cause cancer? • Abnormal cell cycle - Leads to more cells in the tumour - Missed checkpoints permit further chromosomal aberrations • Abnormal cell death - Loss of control of cell number - Apoptosis normally kills dangerous cells • Abnormal cell differentiation - Cell division normally stops with differentiation - Undifferentiated cells may live longer and thus acquire additional mutations • Abnormal cell-cell interactions - Low cell adhesion contributes to metastasis 26 26 Cancer progression involves new mutations that promote the next stage Normal Polyps normally promotes cell differentiation 27 27 Loss of polarized epithelial structure can contribute to tumor metastasis green cells spreading Tumours grow and spread Tumours grow but stay in place ras oncogene alone Tumours grow and spread ras oncogene plus polarity gene mutations ras oncogene plus polarity gene mutations Mutations in epithelial polarity genes induce metastasis (arrows) of Drosophila tissues expressing activated ras (Pagliarini and Xu, 2003; Brumby and Richardson, 2003) 28 28 How can we prevent and cure cancer? What causes the mutations leading to cancer? Reduce environmental carcinogens. DON’T SMOKE! What genes are mutated? How do the mutated genes promote cancer progression? 29 29 How can we prevent and cure cancer? What causes the mutations leading to cancer? Reduce > environmental carcinogens DON’T SMOKE! What genes are mutated? How do the mutated genes promote cancer progression? 30 30 Gleevec: a drug treatment for chronic myelogenous leukemia targeting Bcr-Abl fusion of 1 chromosome with another chromosome kinase that is always on! 31 31 Cancerous cells have disrupted DNA Karyotype of a cancer sample with many chromosomal abnormalities Karyotype of a tissue sample with a normal complement of chromosomes 32 32 How are oncogenes produced? e.g. the Philadelphia chromosome 33 Bcr-Abl is an oncogene that causes chronic myelogenous leukemia 33 Gleevec: a drug treatment for chronic myelogenous leukemia targeting Bcr-Abl Gleevec outcompetes the ATP ATP pocket 34 34 Multi-drug treatments may be more effective than sequential treatments for cancer therapy 35 35 Lecture 12 reading 1205-1210 1220 1224-1225 1231 1234-1239 1241-1244 1249-1250 1254-1256 1260-1265 the emperor of all maladies a biography of cancer 36 36 ...
View Full Document

This note was uploaded on 04/03/2012 for the course BIOLOGY BIO230 taught by Professor Harris during the Fall '11 term at University of Toronto.

Ask a homework question - tutors are online