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Lecture 21

BMS 860 Lecture 21: Cancer Notes 21

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Ryerson University
Biomedical Sciences
BMS 860

Lecture 21- Cancer treatments Fighting the monster- Greek mythology • One of Hercules' labors was to kill a poisonous serpent with 9 heads • Took a friend with him, each time he smashed a head, 2 new heads would grow • Friend would burn neck of head th • 9 head was immortal, but he buried it Cancer Prevention • Steps a person can take to minimize their risk of developing the disease • avoiding the causes of cancer o ex. smoking, alcohol, UV, cancer causing virused, chemical carcinogens, reduce intake of red meat and saturated fats • blocking the development of cancer o Eating fruits and vegetables (phytochemicals) o Chemopreventation targets (i.e aspirin and tamoxifen) o Limiting the number of calories in the diet and regular exercise o Immunization (i.e. HPV vaccine) • The success rate for current cancer treatments are strongly influenced by the stage at which the disease is diagnosed. If cancers are routinely detected at an earlier stage, many cancer deaths could be prevented. Early Cancer Detection Prevents Cancer Deaths • Pap smear test for cervical cancer detection- 75% decrease in cervical cancer deaths • Mammography screening for breast cancer detection- 30% decreased risk of dying from breast cancer (women over 50) • Colonoscopy for colorectal cancer detection • Prostate Specific Antigen Test for Prostate Cancer Issues with Early Cancer Detection • Screening tests must exhibit sufficient sensitivity and specificity to minimize the potential problems that would be created by incorrect test results o Sensitivity: what percentage of the people with a given type of cancer will have their cancer detected when a screening test is used? ▪ If test is not very sensitive = false negative results o Specificity: what percentage of people who do not have cancer are correctly identified as being free of the disease? ▪ If test is not very specific = false positive results • Research says 30% men prostate detected have tumors that would not otherwise be detected and do not need to be treated- sometimes don’t need to treat early cancers, death from surgery Cancer treatments depend on cancer diagnosis • Diagnostic strategies for cancer detection o Blood test, imaging examinations, biopsy followed by histopathological analysis, molecular testing Cancer diagnosis • Should a diagnosed tumour be treated? • What available therapies are appropriate for the subtype of tumour that has been identified? Cancer diagnosis involves tumour staging: • Series of criteria to estimate how far a person’s cancer has progressed at the time of diagnosis • TNM staging system: o T (tumour size); N (lymph node); M (metastasis) o Cancers are assigned a stage number based on: ▪ How large is the tumour and how far has it invaded into surrounding tissues? ▪ Are lymph nodes “positive” for cancer cells? ▪ To what extent have cancer cells metastasized to other organs? o Tumour staging guides prognosis and treatment Diagnosed tumours fall into three broad categories: • Indolent tumours (localized)- low invasive tumours with low metastatic potential during the lifetime of the patient (incidentalomas) • Intermediate grade tumours (regional)- with the potential to disseminate but can be excised or treated with cytotoxic therapies before dissemination occurs and metastases form o Intermediate grade tumours are priority for cancer treatment • Highly invasive tumours (distant)- with high probability of metastases formation Cancer Treatments • Surgery, radiation, chemotherapy, molecular targeted therapies • Emerging treatments: angiogenesis, immunotherapy, epigenetic targeting Surgery • The oldest approach of treating cancer • 1890 the first mastectomy – complete removal of the breast in women with breast cancer • Type of surgery for cancer treatment: o Scalpel surgery o Laser surgery (cervix, larynx, liver, skin, rectum- highly focused beam of laser light o Electrosurgery (skin and mouth)- high frequency electrical current o Cryosurgery (prostate cancers, dysplastic cervix)- liquid nitrogen spray to freeze or kill cancer cells • Beneficial when the tumor has not spread to distant sites Surgery in Breast Cancer Treatment • Radical Mastectomy (Dr. William Halsted) o Removing of the entire breast, underarm lymph nodes, and both chest muscles, without cutting into the tumour at all. o Standard operating procedure from 1900-1970. o Only 52% of women undergoing radical mastecomy lived three years without a local or regional occurrence. o Notion was that cancer progresses slowly • Lumpectomy (1985: Dr. Bernard Fisher) o Surgical removal of the tumour and some of the normal tissue surrounding it o First to show that less-invasive lumpectomy surgery treated breast cancer just as effectively as did disfiguring radical mastectomies. o Pioneered the multicenter randomized clinical trial as a set standard for the scientific evaluation of therapy for many other diseases. o suggested that cancers enter blood early and become circulating tumor cells Radiation Therapy • Surgery is not always sufficient or practical o Brain tumours – surgery could cause brain damage o Leukemias – cancer in bloodstream o Post-surgery recurrence • Radiation therapy can be used as first line therapy or adjuvant (post-surgery) o High-energy X-rays to kill cancer cell • Radiation kill cancer cells in two ways: o P53 activation and activation of cell death by apoptosis (p53 wild type tumours) o Chromosomal damage severe enough to prevent cells from progressing through mitosis and the cells die while trying to divide ▪ Cells that divide more frequently (cancer cells) are more susceptible to mitotic death than cells that divide less frequently (normal cells) • Cancers very responsive to radiation: o Hodgkin’s disease, neuroblastoma. retinoblastoma • Cancers poorly responsive to radiation: o Melanoma, glioblastoma, kidney cancer, pancreatic cancer Chemotherapy • Use of drugs that either kill cancer cells or interfere with the ability of cancer cells to proliferate • Goals of Cancer Chemotherapy o Cure, prolong survival, palliation (decrease pain) • Type of Chemotherapies o Combination Therapy o Adjuvant Therapy (administered after primary therapy) o Neo adjuvant Therapy (given before surgery to reduce tumour size) • Drugs used in cancer chemotherapy: o Antimetabolites, alkylation agents, antibiotics, hormonal therapy Chemotherapy: antimetabolites • Molecules that resemble substances involved in normal cellular metabolism. • Enzymes bind to antimetabolites in place or normal molecules, disrupting essential metabolic pathways and poisoning the cell. • Most of the antimetabolites used in cancer therapy disrupt pathways required for normal DNA synthesis and repair. Dr. Sydney Farber: The Father of Modern Chemotherapy • A pediatric pathologist interested in finding leukemia treatments. • before WW2, a disorder caused by vitamin B12 deficiency characterized by the overwhelming presence of immature red blood cells in the bone marrow, a feature that resembled leukemia • At the time, an essential food chemical, folic acid, was found to cure similar anemias seen in infancy and pregnancy o Folic acid concentrate inhibited sarcoma mice (Dr. Lucy Wills). • Infused children with synthetic folic acid. • Folic acid “accelerated” their disease and killed them in a matter of days to weeks. • Farber hypothesized that an “antifolate” would cure the children of leukemia. • When these children were given agents that blocked the utilization of folic acid (aminopterin), their tumors were extinguished albeit temporarily. • Disease did come back but showed that remission is possible Chemotherapy: alkylating agents • Induce covalent modifications of DNA • Disrupt normal DNA function by crosslinking the two strands of the DNA double helix – two strands are unable to separate and DNA replication cannot take place • Examples of alkylating agents: o Nitrogen mustard (mechlorethamine) – Hodgkin’s lymphoma ▪ chemical weapon used in WW2, had anti cancer effects o Platinating agents ▪ DNA-crosslinking agents containing platinum ▪ Cisplatin – cures 90-95% of testicular cancer; also used for treatment of ovary, breast, pancreatic, lung cancers • growth of bacteria after applying electric current- ammonium chloride in media formed cisplatin and cross linked with DNA, stop cells from dividing • cisplatin attaches to guanine of DNA, DNA will bend 30 degrees, leads to DNA damage and apoptosis Chemotherapy: antibiotics • Anticancer substances produced by bacteria • Many antibiotics for cancer treatme
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