What is Cancer? - California State University, Northridge

1 1 what is cancer ? cancer is a genetic disease: Inherited cancer Sporadic cancer cancer typically involves a change in geneexpression/function: Qualitative change Quantitative change Any cancer causing genetic alteration typically results inloss of cell growth is Cancer? 3 what is Cancer? Malignant Vs. Benign growth Benign: called a tumor Well circumscribed, slow growing, non invasive, non metastatic. Malignant: called a cancer Not well organized, irregularly shaped, fast growing, infiltrativegrowth, metastatic. Initial stages of malignant cancer may typically showbenign growth; further accumulation of mutations may make it Benign tumors aretumors that cannotspread by invasionor metastasis;hence, they onlygrow locally. Malignant tumorsare tumors that arecapable of spreadingby invasion andmetastasis.

2 By definition, theterm " cancer "applies only tomalignant Vs. Malignant TumorsFrom: National cancer Institute : cancer arises from a loss ofnormal growth control. In normal tissues, the rates ofnew cell growth and old cell deathare kept in balance. In cancer , this balance isdisrupted. This disruption canresult from uncontrolled cellgrowth or loss of a cell's ability toundergo "apoptosis." Apoptosis, or "cell suicide," is themechanism by which old ordamaged cells normally : Loss of CellGrowth ControlFrom: National cancer Institute : of Cell Cycle Regulation at CheckpointsAccumulation of DNA damage, errors inreplication, introduction of mutations,chromosomal translocations, aneuploidiesIncreased growth rate, escape fromapoptosisNormal CellTumor CellTumor Cell Formation7 Properties of cancer Cells cancer cells exhibit several characteristics that are distinct fromnormal cells.

3 Multiple changes are involved in the conversion of a normal cellto a cancer cell: Autocrine stimulation; grow in the absence of growth factors Lack of gap junctions; lack of contact inhibition Resistance to cell death; persistent telomerase activity Rapid growth; overtake population, invade other tissues. Angiogenesis Clonal nature of cancer Genomic Instability: Accumulation of successive mutations A germline mutation causes a hereditary cancer . A somatic mutation causes a sporadic ofCancer Cells:Autocrinestimulation,Lack of contactinhibition,Lack of celldeath,Lack of gapjunctions9 Properties of cancer Cells: Lack of contact inhibitionNormal skin cellsGrow in monolayerSkin cancer cellsDo not grow in monolayerPile up on each other10 Properties ofCancer Cells:Lack ofApoptosis(Programmedcell death)11 Properties ofCancer Cells:GenomicInstability12 Properties of cancer Cells:Changes that produce a potential for immortality Loss of limitations on the number of cell divisions Ability to grow in culture normal cells do not grow well in culture Restoration of telomerase activityFeature Figure c13 Properties of cancer Cells.

4 Changes that enable tumor to disrupt local tissue and invadedistant tissues Ability to metastasize Angiogenesis secrete substances that cause blood vessels togrow toward tumor Evasion of immune surveillanceFeature Figure d14 Properties of cancer Cells:clonal descendents of one cellFig. cancers result from exposures to mutagens If one sib or twin gets cancer , other usually does not Populations that migrate profile of cancer becomes more like peopleindigenous to new location16 cancer develops over timeFig. began frequent smoking after 1940 Females began frequent smoking after 196017 cancer develops over timeFig. accumulate over timeIncidence of cancer increases with age18 Sporadic Vs. Familial cancer Familial: inherited form. The family has a predisposition through agermline mutation.

5 Increases the probability that further mutations will occur. Sometimes the initial germline mutation may be responsiblefor different cancers: same family may have individuals with breast, bone, lung, ovariancancer because of a single inherited germline mutation: : p53. Sporadic cancers: new mutations arising in somatic cells of the body. Could result in any type of cancer , depending on the where themutation CancerInheritance of a mutation in a " cancer protection" gene in a germcell (egg or sperm). The offspring will have both a faulty copy and acorrect copy of the " cancer protection" gene in all the cells of theirbody, and will be predisposed to develop : The Center for Genetics Education Website: CancerMutations that occur during life in the body cells (somaticmutations) such as the cells of the breast are confined to thebreast tissue.

6 These mutations will not be passed on to the : The Center for Genetics Education Website: and cancer Two classes of genes are mutated frequently in cancer : Tumor suppressor genes: loss of function mutations. Normal function is to prevent cell proliferation. So-called cancer protection genes Protooncogenes: gain of function mutations. quantitative change in expression of these genes common in cancer Normal function is to promote cell Suppressors vs. Oncogenes Oncogenes dominantmutations Mutant tumor-suppressor genes recessivemutations232425 Multistep Nature of cancer cancer develops progressively as mutations accumulate. Experimental evidence in mice with either the ras OR the mycprotooncogenes mutated: fewer tumors develop than when BOTH genes are mutated.

7 Mice with only one allele of the tumor suppressor p53 mutated arenot as cancer prone as when both alleles are mutated. Hereditary adenomatous polyposis or Familial adenomatouspolyposis (FAP): a typical example of the multi-step pathway for Nature of Cancer27 The Multi-StepModel forColon Cancer28 The Multi-Step Model29 Genomic Approaches to CancerDiagnostics and Therapies cancer Diagnostics Goal: Properly classify the type of cancer To properly treat that specific type Usually done by morphology, Certain tumor surface markers, and Identification of translocations Now, genomic approaches can help Determine the gene expression array of the tumor Compare to tumors with known patient outcome Gene profiling Example: Non-Hodgkin Lymphoma, DLBCL30 Non-Hodgkin Lymphoma, DLBCLN ormal B lymphocytesDiffuse Large B Cell Lymphoma31 Non-Hodgkin Lymphoma, DLBCLH igher patient survival rate correlates with GC B-like RNA profile32 Homework Chapter 22 # 15, 16.