Lecture 11: Oncology/Neoplasia

Lecture 11: Oncology/Neoplasia Cancer Overview · cancer is caused by altered cell differentiation and growth. New growths are neoplasia · cancer is not one disease; it can stem from any organ of the body ↳ most common is breast, prostate, lung, and blood cancers (hematologic) · causes: environment, immunosuppression, genetics, hormones, disease (chronic inflammation) · There are 2 types of neoplasms: ① Benign (non-cancerous) ② Malignant (cancerous) ↳ uncontrolled proliferation ↳ uncontrolled proliferation ↳ slow growing ↳ fast growing ↳ non invasive ↳ invasive ↳ enclosed ↳ not enclosed ↳ only removed if it oppresses the tissue of origin ↳ ALWAYS requires treatment - - Cancer Cells vs. Normal Cells · normally cells self-destruct when there is an error in the DNA, and is then removed by phagocytes · uncontrolled proliferation → keeps on growing · de-differentiation → loss of functioning · invasiveness → can spread from primary location ↳ regardless of where it spreads you must treat it from its primary location · metastases (mets) ↳ cancer cells break away from primary site, travel through blood or lymph, and form new tumors (metastatic tumors) ↳ note: metastatic tumors are the same cancer as the primary cancer Cancer Types: ① Solid · abnormal tissue mass · difficult to assess in blood (only minor changes at first) · may release abnormal chemicals detectable in blood eg. prostate specific antigen in prostate tumors ② Hematological · blood or bone marrow cancer (no mass) · detectable changes in blood eg. Leukemia or Lymphoma Cancer Testing: · Bloodwork ↳ CBC differential · Blood smears ↳ looking for abnormal cell structures · Antigen testing eg. C-reactive protein · CT scan, MRI, X-rays, ultrasounds... · Biopsies Stages · Stage 1: ↳ no lymph involvement ↳ no mets ↳ tumors less than 2 cm · Stage 2: ↳ local lymph involvement (proliferation) ↳ no mets ↳ tumors less than 5cm · Stage 3: ↳ nodal involvement ↳ no mets ↳ tumors over 5cm · Stage 4: ↳ nodal involvement ↳ mets ↳ tumors greater than 5 cm Cancer Therapies · goal is to isolate and damage only neoplastic (cancer) cells ↳ however it may damage surrounding tissues · combination therapy is most effective! · surgery (removal) · radiation (direct cellular injury) · chemotherapy (anticancer drugs) ↳ targets different phases of the cell life cycle ↳ neoadjuvant: chemotherapy given prior to surgery (decrease size of tumor) ↳ adjuvant: given after surgery, or in combination w/radiation Radiation · Radiation causes damage to cells by directly fracturing their DNA using gamma rays · radiation is directed at the tumor site through different procedures: ↳ external beam ↳ brachytherapy (inserted catheter/device to direct radiation) ↳ radioembolization (radioactive beads are placed into blood vessels to block the blood flow that feeds the tumor) ↳ radioisotope (systemic radiation medication) eg. radioactive iodine targets only thyroid cancer · side effects: local skin irritation, local hair loss, inflammation, etc. Guiding Principles of Chemotherapy · curative: achieve total cure by killing all cancer cells ↳ early diagnosis and treatment · control progression: prolong life by stopping or slowing growth of particular malignancies · palliative: decreases symptoms from the cancer to enhance or improve quality of life Chemotherapy Agents 1. Target DNA formation/repair 2. Target hormone processes ↳ receptor agonists and antagonists 3. Immunotherapy ① DNA Targetting · Alkylating drugs: nitrogen mustards ↳ react w/proteins that bond to form DNA helix and adding an alkyl group that prevents proteins from lining up ↳ non-cycle specific · Antimetabolites: methotrexate ↳ disrupts metabolic processes by mimicking essential cellular components that interfere W proper functioning and growth ↳ S-phase · Cytotoxic antibiotics: Bleomycin ↳ bleomycin yields free radicals leading to oxidative stress damage to the cancer ↳ often used in synergy/combination treatment ↳ G2 phase · Vinca Alkaloids → allergy? ↳ disrupts assembly of microtubules during cell division ↳ M-phase ② Hormonal Anticancer Agents · Estrogen-like ↳ estrogen receptor agonist ↳ counteracts endogenous testosterone ↳ efficacy: prostate cancer · Tamoxiflen ↳ estrogen receptor antagonist ↳ prevents estrogen-stimulating growth ↳ efficacy: estrogen-positive breast cancer Side Effects of Treatment ③ Immunotherapy · Immunostimulants ↳ stimulates immune system against certain tumor cells ↳ drug: interferons, interleukins · Antibodies 1) Monoclonal antibodies ↳ marks cancer cells to enhance and direct immune response 2) Immune "check-point" inhibitors ↳ cancer cells deactivate the immune response, this drug reactivates the immune response to activate and locate cancer - - Extravasation · extravasation happens when the IV leaks out the toxic substance · vesicants: drugs that can cause blistering, severe tissue injury, or necrosis · irritants: drugs that may cause inflammation and/or pain but NOT necrosis · non-irritants: good drugs Chemo Attacks more than Cancer · fast-dividing cells are most prone ↳ blood cells (bone marrow suppression) ↳ GI cells ↳ hair follide cells ↳ hepatic cytotoxicity · Hemopoetic agents are used to counteract severe effects of toxicity by stimulating formation of RBC, WBC, and platelets Cancer Cell Resistance · primary resistance: therapy does not work even from the beginning · acquired resistance: adaptation leads to therapy becoming less effective · Resistance techniques: ↳ reduced uptake of drug ↳ enhanced regenerative enzyme production so cancer repairs itself ↳ altered enzyme functioning ↳ deactivation of drug Alternative Therapies · high dose IV Vitamin C (absorbic acid) ↳ reduce oxidative stress ↳ forms new collagen to prevent malignant infiltration ↳ carries H202 generating free radicals against cancer cells · Vitamin D ↳ maintains calcium and phosphorus levels in blood and bone to help w/immune system functioning · Cannabis ↳ THC may down-regulate and control cell invasion ↳ THC may promote cell growth in cancers without cannabinoid receptors · Tumeric ↳ anti-inflammatory and anti-oxidant effects to enhance apoptosis ↳ may have chemo/radiosensitivity effects