Cancer and Neoplastic Disease Lecture 10 PDF

Cancer and Neoplastic Disease Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com. Learning Objectives ▪ Compare the general characteristics of benign and malignant tumors. Explain how tumors are named. ▪ Differentiate between infiltrating and in sit...

Cancer and Neoplastic Disease Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com. Learning Objectives ▪ Compare the general characteristics of benign and malignant tumors. Explain how tumors are named. ▪ Differentiate between infiltrating and in situ carcinoma. ▪ Understand the role of activated oncogenes and disturbance in suppressor gene function on the pathogenesis of tumors. ▪ Understand how susceptibility to cancer can be inherited. ▪ Explain the mechanisms of the body’s immunologic defenses against tumors. ▪ Summarize the principal modalities of tumor treatment, including physiology, advantages, disadvantages, and common side effects of each technique including immune checkpoint inhibitors. ▪ Explain the role of the Pap smear in early diagnosis of neoplasm. ▪ Compare the incidence and survival rates for various types of malignant tumors. Explain the mechanisms of late recurrence. Describe the role of adjuvant therapy in preventing late recurrence. Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Describe the stepwise process of the development of malignancy Cancer All cells have mechanisms to control (promote/inhibit) growth ▪ Stable, but can renewal/multiply rapidly when stimulated (Hepatocytes, T cells) Most times not replicating at all ▪ Permanent, no renewal/ regenerative capacity (Cardiac muscle) and neural cells Cardiac cancer - rare since cells are not dividing cancers of brain usually result from supporting cells rather than neurons since they don’t divide Tight regulation of cell cycle ensure cells “stay in their lane” Loss of control – development of cancer – development from a single clone that escapes cell cycle regulatory control Not a population of cells if earlier up (ex. Stem cell) there can be broad type of phenotype advanced cancer: two cells that may have developed at different times Cancerous tumors are characterized as: ▪ Benign versus malignant ▪ Solid (embedded, but distinct from tissue) versus invasive (mixed within host tissue) ▪ In situ (one location where first formed) versus infiltrating (growth spread into surrounding tissue) Cause damage here Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Constant renewal (hair follicles, gut lining) often express markers that we see in fetal cells and stem cells • ex. Epithelial cell wouldn’t look much like epithelial cell under the microscope ex. Cell from fat cell still looks like a fat cell Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Cant see border in them Benign Versus Malignant Pushes on brain tissue —> damages it and causes problems Must consider damage to tissue replaced and damage from tumor volume/position may be hard to resect —> depending on where it is, you might cause more damaging removing it than damage it causes itself Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Benign ▪ Growth rate: Slow ▪ Growth character: Expansion ▪ Tumor spread: Remains localized – can still do damage through growth (brain tumor) pushes – not infiltration ▪ Cell differentiation: Well-differentiated cells (closely resemble cells of origin) – primary factor to classify benign vs metastatic FIGURE 7-3 Low-magnification photomicrograph of benign breast tumor (fibroadenoma). Note the sharp demarcation between the tumor and surrounding breast tissue (arrow). Courtesy of Leonard V. Crowley, MD, Century College. Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Clear border - can clearly see where tumour is (in this case, breast tissue) • easy to resect for surgeon No clear line or demarkation, all sorts of area of infiltration —> potential for metastasis white area: tumour cells that have infiltrated the lymph nodes Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Malignant ▪ Growth rate: Rapid ▪ Growth character: Infiltrating ▪ Tumor spread: Metastasis by bloodstream or lymphatic channels to establish secondary sites that can also grow and spread (colon spread to liver, breast/lung to brain) ▪ Degree of metastasis often defines cancer staging ▪ Cell differentiation: Poorly differentiated cells Tumor Classification- Benign Tumors Simply named with prefix-(cell of origin) and suffix (oma) Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Tumor Classification – Malignant tumors Carcinoma: Involves epithelial tissue ▪ Arise from surface, glandular or parenchymal epithelium ▪ Most common: 85% of all tumors found in skin, large intestine, glands, stomach, lungs, prostate ▪ Metastasis: Principally through lymph vessels ▪ Subtypes: further classified by cell type or origin and organ ▪ Adenocarcinoma (ie of pancreas – glandular/ secretory cells) ▪ Squamous cell carcinoma (skin) Bulk of cancers - not just skin tissues in skin don’t have direct blood flow carcin - tells you it is epithelial Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Many types, mostly fall into 3 groups (carcinoma, sarcoma, leukemia/lymphoma) Tumor Classification – Malignant tumors Moves a lot faster than lymph Leukemia: Neoplasm of blood cells ▪ Usually does not form solid tumors ▪ Instead, proliferates diffusely within bone marrow, overgrows and crowds out normal blood-forming cells ▪ Neoplastic cells spill over into the bloodstream, and large number of abnormal cells circulate in the peripheral blood ▪ If they populate LN and spleen: lymphoma (T cell/B cell) pancytoema - lack of development of blood cells Will potentially be centered in lymph node and periphey - compromised immune function Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Sarcoma: Arising from connective tissues, such as fat, bone, cartilage, muscle ▪ Arise from endothelium, mesothelium ▪ Less common, but spreads more rapidly ▪ Little differentiation; anaplasia (lack of form) ▪ Metastasis: Bloodstream ▪ Fibrosarcoma (fibroblasts) myosarcoma (muscle) Neoplasm Development Stepwise process that involves ongoing series of genetic changes over time (not just one event) has good prognosis and slow development even if you have cancerous causing strain of HPV Cervical cancer – example: commonly begins in cervical cells in the transformation zone (two types of cells meet/border) cells inside cervix create border in vaginal canal —> becomes exposed as women mature sexuallyand is an area of high cell division —> highest risk of getting HPV infection here —> zone tested by regular PAP smearing Columnar epithelium (cervical canal leading to uterus) and squamous epithelial cells of cervix exposed in vaginal canal – particularly during sexual maturation Multiple insults to way cell grows - if not repaired and corrected —> increased risk fir developing another —> biggest risk factor for cancer is age Columnar cells exposed to acidic environment of vagina are prone to metaplasia (conversion to a different cell type) and become squamous cells (dysplasia) This process is susceptible to neoplasia and develop Cervical Intraepithelial Neoplasia (CIN) Histology section Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Earlier stages have chance of resolution, control by immune surveillance/destruction Growth of Neoplasms Cancers do not usually result from mutation of a single gene Combination of genes promote division when mutated - cause cells to proliferate rapidly If they get mutated to the point where they can’t stop cell cycle —> risk of cancer some oncogene and tumour suppressor genes mutated that allow cell to proliferate —> redundancies Although most cancers are monoclonal - Derive from a single cell some cancers can have considerable heterogeneity if they derive from a stem cell ▪ Stem cell: early in development, has the potential to become many different types of cell Very diverse looking cancers —> very dangerous ▪ Results in tumor with high degree of heterogeneity Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Cancers occur as the result of multiple genetic insults to the genome ▪ Activation of oncogenes ▪ Loss of function of one or more tumor suppressor genes ▪ Additional random genetic changes Tumor Blood Supply and Necrosis often not enough Fast growing neoplasms may outgrow blood supply – can be used as therapeutic target ▪ Malignant tumors frequently induce new blood vessels to proliferate in adjacent normal tissues to supply the demands of the growing tumor (angiogenesis) ▪ Malignant tumor may outgrow its blood supply; the part of the tumor with the poorest blood supply undergoes necrosis ▪ In tumors in the lung, blood supply is best at the periphery of the tumor and poorest at the center (central necrosis) Tumour isn’t getting blood flow in middle —> starts dying off • can get anemia and chronic bleeding Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Tumors derive blood supply from tissues they invade ▪ If tumor is growing outward from an epithelial surface, such as the colon, the best blood supply is at the base and poorest at the surface (peripheral necrosis) Areas far away form contact of tissue will have necrosis ▪ Often, small blood vessels are exposed in ulcerated parts of a tumor, leading to anemia from chronic blood loss ▪ An ulcerated tumor may be the source of a severe hemorrhage central area is necrotic and dying Upper area not in contact with the tissue and getting enough blood supply Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Genetic Change in Neoplastic Disease ▪Tends to occur in genes governing cell cycle (growth/death – inhibition or promotion) and DNA repair ▪Can be caused by: Radiation, carcinogens, viruses – failure of DNA repair / fidelity mechanisms Ex. HIV causes cancer because it integrates into genome randomly if it intersects oncogene or tumour suppressor gene environmental factors ▪Failure of Immune defenses ▪Over time these can accumulate (age dependent) autoimmunity is just bad luck - random risk and accumulation ▪Can also be inherited susceptibilities to developing cancer Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Alteration of genes so cell no longer responds to normal control mechanisms – uncontrolled proliferation Genetic Change Rampant spread and cell divisions Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Cancer promoting genes associated with Carcinogenesis are classified into 3 groups: aggressive Fragmented chromosome with translocation Proto oncogene abl (22) becomes fused with bcl (9) results in uncontrolled and overactive tyrosine kinase that stimulates rampant cell growth – very aggressive cancer use inhibitors for this type of cancer to try to stop its spread Pro-apoptoic • makes cells grow quickly and can be turned off to stop apoptosis Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Proto oncogene: Philadelphia chromosome – seen in chronic granulocytic leukemia (translocation of pieces of chromosome 9 and 22) Genes Regulating Apoptosis ▪Influence survival time of cells ▪Cells have pro and antiapoptotic proteins ▪If gene fails or over regulated - loss of apoptosis control ▪ Cells continue to accumulate ▪ Cells eventually form a tumor Most commonly effects seen with genes that promote cell survival/growth (BCL-2, Bcl xl, MCl-1) Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Programed cell death If one tumour suppressor gene is mutated, other one can continue to function and we don’t notice • both must be deactivated, predominates in cases where once defective gene is inherited • Function by preventing DNA replication and completion of mitosis • Normally suppress cell proliferation • Loss of function by mutation may lead to unrestrained cell growth Example: Retinoblastoma DNA repair: both must be deactivated (similar susceptibility to tumor suppressor genes) • Replication on going repair can be compromised Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Tumor suppressor genes: Genes (expressed in pair of homologous chromosomes) that inhibit/control cellular division/proliferation Genetic Changes Leading to Cancer tumour supressor Initial mutation destabilizes genome and allows the next event…. In this example colon cancer develops after the Accumulation of: • 3 tumor suppressor genes (APC, DCC, p53) • Activation of an oncogene (Ras) Increased growth inside intestines • creates susceptibility (increased proliferation of cells) —> uncontrolled growth Tumour suppressor important in DNA repair chronic inflammation - causing increased cell division FIGURE 7-16 Somatic mutations and cell morphology in the progression of colon cancer. Photographs courtesy of Dr. Kathleen R. Cho, University of Michigan Medical School. Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com In most cases cancers do not result from single Mutation event, but result of multiple accumulated events over time. Tumors Caused by Viruses Used in lab to immortalize cell lines in the lab - still exists in nature Leukemia and lymphoma: T cell leukemia–lymphoma virus (HTLV-1) that is related to the AIDS virus (tax onocogene) Kaposi sarcoma: Human herpesvirus 8 (HHV-8) Certain strains Condylomas (warts): Papilloma virus (HPV); predisposes to cervical carcinoma not virus directly Chronic viral hepatitis: Hepatitis B and C viruses (chronic inflammation/repair) Caused by liver Nasopharyngeal carcinoma: Epstein-Barr virus also causes infectious mononucleosis Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com once you have them - have them forever if exposed when young - doesn’t cause problems but when old, you have decent change of getting it with extended disease where you are sleepy and tired for couple of months • can infect epithelial cells Cancers caused by viruses can be a targeted effect of viral infection (HTLV) or a random side effect from chronic inflammation (HCV) or DNA insertion (HIV) In contrast – chemical carcinogens are caused by random mutations and failure of DNA repair mechanisms Failure of Immunologic Defenses ▪ Failure to control viral replication and/or recognize tumor cells as foreign (they are self after all!) ▪ Immune system can detect and destroy cancerous cells (CD8 T cells, NK cells) Recognize proteins that aren’t self and destroys them ▪ Patients with severe immunodeficiency at increased rick for blood, skin cancer (Kaposi sarcoma – HIV) can secrete factors - create environment where immune system passes over them ▪ Cancer cells have many defenses to protect themselves from immune attack (decreased MHC expression, or exhibit immune suppression functions) When attacking cancer, we are attacking ourselves CD8 don’t engage and recognize protein Immune system doesn’t want to attack self Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Immune checkpoint inhibitors (control immune response) inhibit development of autoimmunity – also interfere with attacking cancer cells Heredity and Tumors Most mutations that cause cancer are not directly inherited. Predisposition results from multifactorial inheritance pattern ▪At-risk individual has inherited set of genes that influence hormonal or enzyme-regulated biochemical process in the body that can increase susceptibility to a specific cancer ▪Example: Breast cancer (autosomal dominant) ▪ 80% to 90% of cases: No family history of the disease ▪ 10% of cases linked to gene mutations ▪ Abnormal BRCA1/2 DNA repair genes – 80% risk of breast cancer by age 90 Get it based on susceptibility Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com not linear Heredity and Tumors Discovery important for screening programs and those who have these genes running in their families Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Inheritance of certain genetic alterations that have increased cancer risk – generally account for a small fraction of cancers ▪ Breast cancer susceptibility genes BRCA1 and BRCA2 ▪ Ph1 chromosome ▪ Multiple polyposis of colon – prone to development of Colon polyps that are prone to malignancy (autosomal dominant) ▪ Neurofibromatosis – increased production of benign tumors of the nerves that have increased risk of malignancy (autosomal dominant) ▪ Multiple endocrine adenomatosis – formation of multiple endocrine adenomas (autosomal dominant) Diagnosis of Tumors ▪Precancerous conditions throat cancer Ppl aged >55 Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪Early recognition – symptoms/screening (age dependent) Precancerous Conditions Intervene before cancer is at later stages where it gets harder to treat part of check-up at the dentist Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Nonmalignant condition with a tendency to become malignant – visual/physical exam ▪ Actinic keratoses: Small, crusted, scaly patches that develop on sun-exposed skin; may develop into cancer if untreated ▪ Lentigo maligna: Freckle-like proliferation of melanin-producing cells that may develop on sun-exposed skin; may transform into melanoma ▪ Leukoplakia: Thick white patches in the mucous membranes of the mouth from exposure to tobacco tars from pipe or cigar smoking or smokeless tobacco (snuff or chewing tobacco) ▪ Leukoplakia may give rise to squamous cell cancers of the oral cavity ▪ Precancerous conditions should always be treated appropriately to prevent malignant change, which occurs in many - but not all cases Precancerous Conditions https://www.skinlaser.com/blog/the-abcs-of-skin-cancer more complicated for internal cancers Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Is it hard to pin border down? Diagnosis of Tumors ▪Complete medical history and physical examination Screening programs need to consider invasiveness/severity, cost/benefits ▪Surface – Visual ▪Orifice – Endoscopy throat, Upper and lower GI, colon screening ▪Internal – CT scan/MRI Full body scan to look for signs of cancer Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪Recognize early warning signs and symptoms Diagnosis of Tumors very elevated -sign of leukaemia, mild elevation - could be sign of infection or cancer Typical for hisotlogy (check) important for prognosis Most brain cancers don’t come from brain but from other organs and spread up to the brain Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Laboratory procedures ▪ Examination of rectum and colon, stomach esophagus (endoscopy) ▪ CBC – elevated WBC in absence of infection ▪ Vaginal examination and Pap smear in women ▪ X-ray studies ▪ Abnormal smear: Slides of abnormal cells shed from surface of tumors ▪ Biopsy – Endoscopic procedures ▪ Cytologic diagnosis: Fine needle aspiration, biopsy (many organs – precise location of tumor by CT, Xray or US) ▪ Histology: Frozen section Slides prepared and stained – rapid histological diagnosis in minutes ▪ Determine primary/secondary - Secondary Brain tumor 4x more common that primary (lung/breast) Photomicrograph of Pap Smear Courtesy of Leonard V. Crowley, MD, Century College. Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com FIGURE 7-17 Photomicrograph of Pap smear, illustrating a cluster of abnormal cells from in situ carcinoma of the cervix. Cells appear much different from adjacent normal squamous epithelial cells. Diagnosis of Tumors ▪ Carcinoembryonic antigen (CEA): Present in amounts related to size of tumor and its possible spread ▪ Produced by most malignant tumors of the GI tract, pancreas, breast Caricigenic tumour being promoted ▪ Alpha fetoprotein: Normally produced by fetal tissues in the placenta but not adult cells; elevated in primary carcinoma of the liver ▪ Human chorionic gonadotropin: Normally produced by placenta in pregnancy; elevated in testicular carcinoma ▪ (PSA test) Acid phosphatase: Normally produced by prostate epithelial cells, may be elevated in prostate cancer can also use for sign of treatment • can monitor and see how low it dropped • this is an example of a cancer that took off again after treatment (picture) Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Tumor-associated antigen tests: Some cancers secrete substances that can be detected in the blood by lab tests Treatment of Tumors – (need to consider Age/Health/success) Surgery – Better success when in benign stage (non-invasive), decreased with malignancy (tumor and surrounding) Not just about treating cancer aggressively - need to consider age and life-span of patient and if the cancer is going to cause problems or not • procedures are complicated, hard on body, have to consider recovery - what is it doing to life quality of patient Yes or no • stage 4 cancer ▪ Staging I-IV – depending on spread (early, localized, regional spread, distant spread) Damage DNA in rapidly dividing cells • can destroy gonads and may cause patient to become sterile —> advised to store eggs/sperm Radiotherapy – cancer is radiosensitive: can be used to reduce tumor size/removal of remaining cells Hormones – Corticosteroids can inhibit growth, some tumors are hormone dependent (Prostate, /Breast – testosterone/Estrogen) Blocking hormones can inhibit ability of tumour to grow Anticancer drugs (chemotherapy) – variety of drugs: goal is to interfere (preferentially) with cancer cell growth and have acceptable damage to non- cancerous cells – work best against fast growing cancers problem is that they are not specific for cancer Adjuvant chemotherapy – used in combination with surgery to remove residual cells that may not be removed/detected If we can characterize the gene Can have precise targets in some cases – but usually broad effects leading to a number of side effects Philadelphia mutation (BCR-ABL cr 22 abnormality) – susceptible to tyrosine kinase inhibitors Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ TNM Classification (T- size 1-4, N spread to regional LN 1-3, M distant metastasis 0-2), useful for Tx and Px Chemotherapy ▪ Course usually lasts 3-6 months with 4-8 cycles of 3-4 weeks (pulsing/ recovery) allow immune system to reconstitute • patients become neotenic • - need time to recover Routine amount depending on outcomes and how effective chemotherapy is ▪ Alkylating agents: Inhibit DNA synthesis, structure or function (DNA replication) Target rapidly dividing cells ▪ Eliminates cells that divide frequently, Inhibit protein synthesis, mitotic spindle (Cell division) ▪ Can also target cancer specific properties like glycolysis (normal cells predominantly use oxidative phosphorylation for energy metabolism - 70/20, cancer – almost all glycolysis) ▪ Susceptible cells and rapidly dividing cells found in ▪ Mouth, skin, hair, bone marrow, digestive tract, kidneys, bladder ▪ Lungs, nervous system, reproductive system ▪ Lymphoid cells particularly vulnerable always developing new cells - toxicity - point where immune system is not properly functioning Sterility ▪ Normal cells recover quickly, side effects disappear gradually Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Induction (1 month intensive) /Consolidation (few months) / Maintenance (2-3 years) high dose Young people survive more as they have more functional thymus and recovery is faster ▪ How soon the patient will feel better depends on overall health, types of anticancer drugs used Side Effects of Chemotherapy ▪ Anemia: Extreme fatigue, weakness, tiredness, paleness, dizziness experienced by more than half of patients; reduces bone marrow’s ability to make red blood cells ▪ Depression: Physical and emotional stress ▪ Diarrhea: Drugs affect cells that line intestines ▪ Hair loss (alopecia) chemotherapy ▪ Infection due to reduced ability of bone marrow to produce white blood cells ▪ Loss of appetite (anorexia), nausea and vomiting ▪ Mouth, gum, and throat problems; sores ▪ Nausea and vomiting Sexual problems ▪ Men: Affects sperm cells; temporary or permanent infertility ▪ Women: Irregular menstrual periods; vaginal infections; menopause-like symptoms Lack of desire/interest Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Constipation: Drugs, decrease in physical activity, unbalanced diet Radiation Therapy in combination, depending on what is done Damages DNA to disrupt growth of cancer Damages DNA by intercalating ▪ More targeted, but tissue around the tumor can be damaged Internal radiation – tablet, liquid (IV) or brachytherapy (implant to deliver radioactive dose directly to tumor) specific and localized ▪ Fewer side effects compared to external Side effects: nausea, fatigues, soreness, lymphedema, hair loss, irritation and damage (specific to region treated) Implants can be in place for days, or permanent – typically used to treat smaller tumors: commonly used for prostate, cervical and womb cancers Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com External beam (most common) 15 min, 5x/week for 3-9 weeks Surgery Need to consider: ▪Resectability of tumor ▪Operability of tumor ▪Other treatment options • Organ transplant/ BMT Bone marrow transplant - can be complicated based on health of patient and whether or not they can tolerate it Goal is to remove tumor and surrounding tissue – often used in combination with chemotherapy Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪Patient health/survivability (risks) Immune system has a number of methods to control cancers: ▪ NK cells can destroy cells expressing stress signals, deficient MHC I expression ▪ Macrophages can destroy tumor cells by phagocytosis ▪ Antibodies to tumor antigens can tag tumor cells for destruction by Macrophages/ complement Cancers do find ways to avoid detection rely on checkpoint inhibitors, decrease MHC1, etc. Immunotherapy – stimulating the bodies immune response to attack cancer ▪ Nonspecific :Cytokines ▪ Specific ▪ Tumor-infiltrating lymphocyte therapy ▪ Tumor vaccines ▪ Tumor antibody therapy boost immune system - cells more easily activated to go into killing mode Boost immune system to get over checkpoints, etc. Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ CD8 (Cytotoxic) T cells destroy cancer antigens presented by MHC I Non-specific Immunotherapy IFN alpha ▪ has general antiviral effects ▪ inhibition of tumor growth ▪ Useful in leukemia, multiple myeloma IL-2 ▪ Stimulates NK cells and Cytotoxic CD8 T cells ▪ Used in metastatic melanoma, renal cell carcinoma Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Use of various Cytokines to stimulate immune system and/or inhibit tumor cells – tends to be less toxic (flu like symptoms): Specific Immunotherapy Immunotherapy targets: excitement about these as there is low toxicity and effective for older patients Take out T-cells and reengineer to target cancer (CHECK) -CAR-T therapy: genetic TCR alteration - Dendritic cell therapy: activation of dendritic cells in presence of tumor antigens Process antigens from tumour, process, put back in body, hopefully they will present antigen and turn on immunity (CHECK) ▪ Anti-tumor vaccines: tumor antigens from patient used to immunize patient against recurring disease after resection ▪ Anti-tumor antibodies: specific antibodies directed against tumor, sometimes linked with antitumor drug (chemo) or toxin (radioactive) ▪ Drugs to remove blockades that are inhibiting immune function: prevents tumor immune suppression functions (CTLA-, PD1, PD-L1) remove checkpoints ▪ Oncolytic viruses (Vaccinia, Vesicular stomatitis virus) : preferentially infects and kills cancer cells, stimulate anti tumor immunity – Attenuation (only grows in cancerous cells, tumor targeting by direct destruction or flagging immune system) Lytic phase —> cell rupture —> effects surrounding tumour cells Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Administration of CTL directed against tumor: cells from patient are removed and primed/reprogrammed to attack tumor – then reintroduced Survival Rates in Cancer Varies widely (from 4% to more than 95%) ▪ Thyroid cancer: 95% 5-year survival rate ▪ Pancreatic cancer: 4% 5-year survival rate ▪ 5-year survival does not indicate cure; some types recur, prove fatal (breast cancer, malignant melanoma) ▪ Tends to improve with increased screening for some cancers ▪ Important to note that 5-year survival rate reflects treatment/ screening success – not cure! Can depend on cell type infected Good prognosis more screening —> more survival rates • mean death is basically identical One in every four people will eventually develop cancer ▪ Lung cancer: Most common cancer affecting males ▪ Breast cancer: Most common cancer affecting females Early diagnosis and treatment may enhance survival rate Tumor may have already spread by time of diagnosis and initial treatment, but metastatic deposits are held in check by immune defense mechanisms Chances for survival significantly reduced after tumor metastasizes to regional lymph nodes or distant sites Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com detected late, not much symptoms until stage 4 Major types of cancer very good prognosis screening and early detection is important for treating disease • NOTE: detecting early gives better survival rate because you haven’t hit that stage yet Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Cancer and Neoplastic Disease Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com.