HLTH 103 Biological Determinants of Cancer PDF

HLTH 103 – Biological Determinants of Health Cancer Outline of Topics  What is Cancer?  Characteristics of Cancer cells  Tumor Types  Processes of Progression  Cancer Cells and Genetics  Risk Factors & Cancer Types  Detection, Diagnosis, Treatment & Prevention Adapted From: Bozzone, Biology...

HLTH 103 – Biological Determinants of Health Cancer Outline of Topics  What is Cancer?  Characteristics of Cancer cells  Tumor Types  Processes of Progression  Cancer Cells and Genetics  Risk Factors & Cancer Types  Detection, Diagnosis, Treatment & Prevention Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press What is Cancer?  ‘Cancer’ derived from Greek word for crab, karkinoma  disease of uncontrolled and abnormal cellular growth  caused by genetic mutations of genes that regulate cell division:  loss of cell-cycle progression  loss of repair mechanisms, i.e., DNA damage repair  loss of cell suicide (i.e., apoptotic) signals  what are the causes of cancer?  external factors, i.e., environment  risk factor: modifiable  internal factors, i.e., inheritance  risk factor: non-modifiable Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press  How Does Cancer Make You Sick?  normally cells are carefully regulated and organized  normally cell proliferation is balanced with cell death, i.e., mitosis vs apoptosis Normal process of cell differentiation results in specialized cells with specialized functions Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Cancer: Tumor Types Tumors can be benign or malignant Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Cancer: Tumor Types Benign:  Benign growth generally have better prognosis.  Typically little to no potential to kill host.  Can be life-threatening due to location.  Does not invade adjacent tissue or spread to distant sites.  Many are encapsulated with connective tissue.  More closely resembles original tissue type  Grows more slowly. Little vascularity. Rarely necrotic.  Often retains original function Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Banasik, Jacquelyn. Pathophysiology, 6th Edition. Elsevier (HS-US), 022018. Cancer: Tumor Types Malignant:  Can kill host if untreated.  Confirmed by invasive or metastasizing nature.  Tissue-specific differentiation (does not closely resemble tissue type of origin).  Greater degree of anaplasia indicates aggressive malignancy.  Grows rapidly.  May initiate tumor vessel growth.  Frequently necrotic.  Dysfunctional. Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Banasik, Jacquelyn. Pathophysiology, 6th Edition. Elsevier (HS-US), 022018. Cancer: Process of Progression - Metastasis  Metastasis: cancer cells enter the bloodstream, producing secondary tumors Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Cancer: Process of Progression Angiogenesis Angiogenesis: Blood vessels are routed to the tumor, depriving normal cells of oxygen Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press  Pathological vs Physiological Tumor Vessels - disorganized - tortuous - leaky - immature - lack proper contacts and interactions Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Jain 2001; Nat Med 7:987 Cancer Cells are different from Normal Cells  Normal cells  Communicate via chemical signals that influence cell division and program cell death  Stop dividing at a certain density  Only divide a certain number of times  Have regulatory mechanisms (cell cycle, hormones, signals) that maintain an appropriate rate of cell division  Remain in one location throughout their lifespan  Cancer cells  Lack effective communication  Keep dividing regardless of density  Are not programmed to die Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Cancer Cells are different from Normal Cells  Contact Independent Growth Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Cancer Cells are different from Normal Cells  Abnormal Growth Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Hanahan & Weinberg, 2000 Hanahan & Weinberg, 2011 Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford Hanahan University Press 2022  Hanahan & Weinberg, 2011 Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford Hanahan University Press 2022 Hallmarks of Cancer Cells  Sustaining proliferative signaling  Evading growth suppressors  Enabling replicative immortality  Deregulated cellular energetics  Activating invasion & metastasis Avoiding immune destruction  Tumor promoting inflammation  Inducing angiogenesis  Genome instability & mutation  Resisting cell death Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Hanahan & Weinberg, 2011 Cancer Cells are different from Normal Cells Classification based on Tissue Type of Origin  “-oma” suffix indicates benign tumor (adenoma).  Carcinomas: arise from epithelial cells that cover external and internal body surfaces (e.g., lung, breast, and colon cancer)  Basal cell carcinoma involves basal cells in base layer of epithelium and rarely metastasizes, but should be removed  Squamous cell carcinoma involves epithelial cells and may metastasize slowly  Sarcomas: solid tumors of connective tissue such as muscle, bone, cartilage, and fibrous tissue (rare in humans).  Lymphomas and leukemias: arise from cells of lymphatic and blood origin, respectively (i.e. hemotapoietic origin; e.g., multiple myeloma, Hodgkin’s) Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Cancer Cells are different from Normal Cells cell division and cell death are cellular growth and division balanced continues regardless of cell damage, i.e., mutation repair mechanisms are intact and detect cellular damage Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Cancer Cells are different from Normal Cells Normal Cells: Cancer Cells:  Growth factors bind to receptors on the cell receptors may be permanently activated  Activate signal transducers to relay signal transducers may be information stuck in an activated state  Activate transcription factors to regulate transcription factors may be gene activity produced, even if preceding steps are absent signals that trigger apotosis (programmed cell death) are ignored Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Cancer Cells are different from Normal Cells Normal Cells:  Checkpoints regulate the timing of cell division  G1 checkpoint : are raw materials available?  M checkpoint : are chromosomes aligned? Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Cancer Cells are different from Normal Cells Normal Cells: Checkpoints  Checkpoints regulate the timing of cell division  G1 checkpoint : are raw materials available?  M checkpoint : are chromosomes aligned? Decision to divide is influenced by: External factors: Environmental conditions Signaling molecules Internal factors: Cell cycle control molecules Checkpoints Cyclin - CDK complexes: Cyclin concentrations vary by cell cycle CDKs are kinases that control cell cycle events Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Divide constantly and rapidly throughout life Skin cells Skin is continually being formed from deep layers of cells. The outermost layer of dead cells is constantly being sloughed off. Most epithelial cells Epithelial cells lining the inner surfaces of body organs, such as the digestive tract and the lungs, are exposed to frequent damage and must be replaced. Bone marrow cells Stem cells in the bone marrow produce red blood cells (R B C s) and white blood cells (W B C s) throughout life. W B C production can be increased as part of the immune response. Spermatogonia (after Spermatogonia divide to produce sperm throughout life in the adult male. The rate puberty) declines with age. Will divide under certain circumstances Liver cells Liver cells don’t normally divide in adulthood but will do so if part of the liver is removed. Epithelial cells Called granulosa cells, epithelial cells surrounding the egg are quiescent for most of adult surrounding the life. They begin to divide as the follicle matures. egg Normally do not divide in adulthood Nerve cells Although there are exceptions, most human nerve cells apparently do not divide in adulthood. Osteocytes Mature bone cells called osteocytes become trapped within the hard crystalline matrix of Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press bone. Cancer Cells are different from Normal Cells Normal Cells: Cell Cycle  G1: primary growth phase, very active growth  S (synthesis): Synthesis of DNA for next cell division  G2 Final growth phase before cell division  M: cell division  M: Mitosis  prophase  metaphase  anaphase  telophase  cytokinesis Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Cancer Cells & Genetics  Cancer cells progress through the cell cycle regardless of checkpoints  Cancer cells have mutated DNA that is passed to daughter cells  DNA mutations alter cell division  If DNA repair doesn’t occur, mutations accumulate  Genetic mutations can increase the risk of cancer Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Cancer Cells & Genetics: Oncogenes Proto-oncogenes are a group of  genes that are normally involved in promoting cell growth, division, and survival  Mutations of proto-oncogenes  Proto-oncogenes regulate cell results in oncogenes that cause division cancer with over-expression and  Mutations result in oncogenes, which remain turned “on”, resulting gain-of-function mutations in uncontrolled division gain-of-function mutations Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Cancer Cells & Genetics: Tumor Suppressors  Tumor suppressor genes encode for proteins that normally halt cell division  regulatory control mechanisms detect cell damage and promote cell death (apoptosis)  tumor suppressor proteins act as "brakes" in the cell cycle, halting cell division when necessary  Mutations alter TSGs, releasing a “brake” (TSG: tumor suppressor gene)  In leukemia, the TSG NF-1 is mutated, resulting in uncontrolled cell proliferation  loss-of-function mutation  gene product is no longer being produced  regulatory control mechanisms to stop cell growth are lost Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Cancer Cells & Genetics Chromosomal Abnormalities  Parts of chromosomes can brake, rearrange, or become lost  May turn on oncogenes or disable TSGs Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press  chromosomal translocation: Cancer Cells & Genetics long arm of chromosome 9 is translocated with long arm of The Philadelphia Chromosome chromosome 22  Patients with chronic myelogenous leukemia (CML) have an unusual, small chromosome  Chromosomes 9 and 22 exchange pieces  Chromosome This places #9 two proto-oncogenes normally contains the ABL-close together, gene which isturning normally them responsible“on” for transcribing a protein kinase that facilitates and controls cell proliferation  Chromosome #22 normally encodes the BCR- gene that is also involved in cell cycle progression  The activity of gene product is normally regulated through the cell cycle, but Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press translocation results in consistent expression Cancer: Risk Factors & Cancer Types  Mutations in DNA accumulate as you age, increasing the likelihood of cancer Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Cancer: Risk Factors & Cancer Types  At least 2/3 of cancers are influenced by factors we can control, i.e., modifiable:  smoking and alcohol  diet and exercise  excessive exposure to UV  Other factors are beyond our control, i.e., non-modifiable:  infections  exposure to carcinogens and pollutants Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press  Cancer: Risk Factors & Cancer Types  Melanoma  Deadliest, but least common of skin cancers  Cancer of the melanocytes  Metastasizes quickly  Observe skin lesions for  A = Asymmetry: two halves of the affected area don’t match  B = Border: irregularity in shape  C = Color: variability or is black  D = Diameter: greater than 6 mm (size of pea) Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press  Cancer: Risk Factors & Cancer Types Lung Cancer  Smoking: leading risk factor  No simple screening test, so the cancer is often more advanced when detected  Early symptoms are nonspecific  Persistent coughing  Bronchitis  Recurrent pneumonia  Voice change  Treatment  Surgery, often combined with radiation and chemotherapy Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Cancer: Risk Factors & Cancer Types  Ernest Wynder study: cigarette smokers are 40X more likely to develop lung cancer  80–90% of lung cancers are attributable to smoking Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press  Cancer: Risk Factors & Cancer Types Colon & Rectal Cancers  Symptoms: blood in stool, rectal bleeding  Risk factors:  Sedentary lifestyle, obesity, smoking, family history, low-fiber diet, high-fat diet  Start as polyps (benign tumors), which gradually become malignant  Screening tests can detect cancer early  Detection of blood in stool specimens  Colonoscopy: examining interior of colon with flexible fiber-optic scope  Treatment: polyp removal, tumor removal Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Cancer: Risk Factors & Cancer Types  35% of cancers can be attributed to diet  5% of prostate and breast cancers in adults are linked to lack of exercise and excess body fat in childhood Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press  Cancer: Risk Factors & Cancer Types Breast Cancer  Early detection is crucial for survival  Mammogram: low dose X-ray used for early detection  Detection of a lump on breast exam  Risk factors  Genetics: two different genes increase risk: BRCAI and BRCAII:  women with mutant forms have an 84% chance of breast cancer  Early onset of menstruation, late menopause  Obesity after menopause  Oral contraceptives  Hormone replacement after menopause Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press  Cancer: Risk Factors & Cancer Types  Cancer of lymphoid tissue  Includes Hodgkin’s and non-Hodgkin’s lymphoma  Symptoms  Enlarged lymph nodes, intermittent fever, itching, weight loss, night sweats  Risk factors  Altered immune function  Transplant recipients  HIV infection  Occupational exposure to herbicides  Treatment: radiation, chemotherapy, bone marrow transplant Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press  Cancer: Risk Factors & Cancer Types Leukemia  Cancer of immature white blood cells in the bone marrow  Risk factors: Down syndrome, exposure to ionizing radiation, benzene, infection with HTLV-1 virus  Childhood forms of leukemia as well as adult forms of leukemia  Symptoms: nonspecific  Diagnosis: blood tests and bone marrow biopsies  Treatment: chemotherapy, or chemotherapy plus bone marrow transplant Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press  Cancer: Risk Factors & Cancer Types Prostate Cancer: most common after age 50  Symptoms  Urination difficulties, blood in urine, pain in pelvic area  Diagnosis  Digital rectal exam  Blood test for PSA (prostate-specific antigen)  Biopsy  Treatment  Surgery, radiation therapy, hormones Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press  Cancer: Risk Factors & Cancer Types  Uterine cancer  Involves the endometrium  Symptom: abnormal bleeding  Risk factors  Early onset of menstruation, late onset of menopause, not having children, estrogen use after menopause  Cervical cancer  Caused by human papilloma virus (HPV) infection  Detection: Pap test  Prevention: Gardasil vaccine  Treatment: surgery, chemotherapy, radiation, hormones Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Cancer: Risk Factors & Cancer Types  Human papillomavirus (HPV): sexually transmitted virus associated with cervical cancer  Early detection of cervical cancer with annual Pap tests Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Cancer: Risk Factors & Cancer Types Scientist Spotlight: Peyton Rous  Won the Nobel Prize for his work with tumorigenic viruses  Extracted liquid from the tumor of a chicken, making sure no cells were present  Demonstrated this was sufficient to cause cancer when injected in a healthy chicken Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press  Cancer: Risk Factors & Cancer Types Bladder Cancer:  Symptoms: blood in the urine  Risk factors  Smoking, urban living, exposure to arsenic in water supply, occupational exposure to leather, dye, rubber  Diagnosis  Microscopic exam of urine for cancer cells  Cystoscopy: direct examination of bladder wall with cystoscope (thin flexible tube with lens)  Treatment  Surgery with chemotherapy Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press  Cancer: Risk Factors & Cancer Types Kidney Cancer:  Risk factors  Genetics, smoking, exposure to certain toxic chemicals, age, gender (female)  No direct screening tests  Usually detected during examination for a renal-related problem  Diagnosis  CT scan or ultrasound  Treatment  Surgical removal of affected kidney Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Cancer: Risk Factors - Radiation  Exposure to UV radiation has been linked to >90% of skin cancers  Protection from sun exposure and avoiding tanning beds minimizes risk Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Cancer: Risk Factors - Workplace Carcinogens and Pollution Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Cancer: Detection  Blood tests  Ultrasound  Biopsy Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press  C: MRI Cancer: Detection CT scan (computerized tomography) MRI (magnetic A: X-ray resonanceB: CT Scan imaging) Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Cancer: Detection Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Cancer: Treatment Surgery: localized tumors Radiation: exposes cancer cells to X-rays Chemotherapy: drugs that inhibit cell division Immunotherapy: the patient’s immune system is used to fight cancer Angiogenesis inhibitors: drugs inhibit growth of blood vessels, tumor unable to obtain nutrients and oxygen Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Cancer: Prevention  Know family history  Get regular medical screenings  Learn self-examination techniques  Avoid UV exposure  Avoid direct sunlight 10 a.m. to 4 p.m.,  sunlamps, and tanning salons  Don’t smoke  Maintain balanced diet, exercise  Avoid excess alcohol  Avoid known carcinogens Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Diagnosis  Diagnosis via grading and staging of tumor is important to predict clinical behavior of malignant tumor and guide therapeutic management  Grading:  Histologic characterization of tumor cells  Degree of anaplasia  3 or 4 classes of increasing degrees of malignancy  Greater degree of anaplasia = greater degree of malignant potential Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Banasik, Jacquelyn. Pathophysiology, 6th Edition. Elsevier (HS-US), 022018. Diagnosis  Staging  Location and patterns of spread within the host  Tumor size  Extent of local growth  Lymph node and organ involvement  Distant metastasis Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Banasik, Jacquelyn. Pathophysiology, 6th Edition. Elsevier (HS-US), 022018. Diagnosis  Staging  Location and patterns of spread within the host  Tumor size  Extent of local growth  Lymph node and organ involvement  Distant metastasis Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Banasik, Jacquelyn. Pathophysiology, 6th Edition. Elsevier (HS-US), 022018.  Diagnosis – Staging – TNM System © N. Jandu From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press 10/30/24 Adapted Banasik, Jacquelyn. Pathophysiology, 6th Edition. Elsevier (HS-US), 022018. Treatment  Early detection is the best for the best possible prognosis  Mainstays of therapy  Surgery  Radiation therapy  Drug therapy/chemotherapy  Emerging therapies  Immunotherapy  Targeted molecular therapies  Stem cell transplantation Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Banasik, Jacquelyn. Pathophysiology, 6th Edition. Elsevier (HS-US), 022018. Check your understanding: After surgery to remove a lung tumor, your patient is scheduled for chemotherapy, which will  A. have minimal side effects.  B. stimulate immune cells to fight the cancer.  C. kill rapidly dividing cells.  D. selectively kill tumor cells. Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Check your understanding: Deficits in immune system function occur in cancer as a result of:  A. chemotherapy  B. cancer metastasis to bone marrow.  C. malnutrition.  D. cancer cell activity.  E. all of the choices Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Check your understanding: Side effects of chemotherapy include (Select all that apply.)  A. bleeding.  B. infections.  C. nausea.  D. anemia.  E. all of the choices. Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Check your understanding: Cancer grading is based on  A. metastasis.  B. local invasion.  C. tumor size.  D. cell differentiation. Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Check your understanding: A primary care provider is attempting to diagnose cancer and is looking for a tumour marker. Which of the following could be a possible marker?  A. Enzymes  B. Antigens  C. Neurotransmitters  D. Erythrocytes Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press Adapted From: Bozzone, Biology for the Informed Citizen, © 2014 by Oxford University Press