BIOLOGY OF CANCER. Definition: Cancer. Why is it Important to Understand the Biology of Cancer? Regulation of the Cell Cycle 2/13/2015

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1 BIOLOGY OF CANCER Why is it Important to Understand the Biology of Cancer? Cynthia Smith, RN, BA, MSN, AOCN Oncology Clinical Nurse Specialist Harrison Medical Center Definition: Cancer Regulation of the Cell Cycle 1

2 Differences between malignant & normal cells Schematic of Cell: Normal or Malignant Targeting Pathways downstream of K-Ras Oncogene in Lung Adenocarcinoma Co-treatment of Hairy Cell Leukemia and Melanoma With the BRAF Inhibitor Dabrafenib The activating BRAF mutation has been identified in many cancers, including: colon & lung adenocarcinomas, papillary thyroid cancer, malignant melanoma & hairy cell leukemia. Malignant melanoma & HCL are of particular interest because of both the high proportion of cases harboring the mutation and the dramatic responses to BRAF inhibitor therapy reported in the literature. Patients with Hairy Cell Leukemia & malignant melanoma present with the BRAF p.v600e mutation, but may be successfully treated for both cancers with the BRAF inhibitor dabrafenib (Tafinlar). Source: 2

3 Intracytoplasmic Signal Inhibition: small molecule inhibitors, mtor Inhibitors, PARP inhibitors and Proteasome Inhibitors Extracelluar Receptor Inhibition via Monoclonal Antibody Mechanism of Action Can we use the photo on page 35 of the new text under this section heading It is a photo from IMER So What Causes Cancer? Carcinogenesis 3

4 Many Cancer Types Caused by Bad Luck of Random Mutations (Source: Science ) Cancer is an insidious disease that often strikes individuals who lack any type of known risk factors, and new research shows that many cancer types can be chalked up to "bad luck. Using a statistical model to measure proportion of cancer incidence across 31 tissue types, Johns Hopkins University School of Medicine researchers found that 22 cancers, (2/3 s of the total reviewed), could be largely explained by the "bad luck" or random mutations that arise during DNA replication in normal, noncancerous stem cells. The remaining 9 cancer types were more attributable to environmental, lifestyle, and hereditary factors. Focus on stem cell division the more divisions taking place e.g. stem cell turn-over, the more prone tissue is to develop cancer Causes of Carcinogenesis 1. Apoptosis Gene (programmed cell death). May be inactivated in cancer. 2. DNA Repair Gene (repairs abnormal copies / signals cell if unable to repair) 3. Proto-oncogene (signals cell to begin replicating, enter cell cycle) 4. Tumor suppressor gene (instructs cell to stop division) 5. Double helix DNA ladder base pair: Adenine + Thymine; Cytosine + Guanine 6. Nucleotide arrangement /order creates genes, which sit on 23 chromosomes New Research: Stress & Inflammation Combine to Fuel Cancer Growth Definitions Stress: Experience of significant or negative life event or an event without effective coping. Psychological / physiologic response to body perceives as a threat. Inflammation: Cellular manifestation stress. Acute, i.e. innate immunity activates immune system to ward off infection or Chronic, i.e. lingering inflammation can predispose individuals to illness such as cancer. Stress & inflammation probably mediate cancer development & progressions. 25% of cancers are associated with chronic inflammation of broad origin. Source: New Research: Stress & Inflammation Combine to Fuel Cancer Growth Many cancer-related deaths caused by treatment resistantmetastases. Stress & inflammation play role in metastatic steps. Body produces pro-inflammatory markers in response to stress. Cytokines (proteins that function as molecular messengers between cells) are such a marker. Cytokines regulate immune responses and inflammation. Two pro-inflammatory cytokines are interleukins and tumor necrosis factor; work by turning on various transcription factors. Inflammation changes tissue homeostasis; this leads to chronic response promoting tumor growth, angiogenesis, invasion & metastasis by activating surrounding stromal cells & recruiting inflammatory cells (e.g. mast cells, neutrophils, leukocytes, natural killer cells). These cells generate reactive O2 & Nitrogen species, activating oncogene & shut off tumor suppressor gene Source: 4

5 Psycho-Oncology Interventions for Managing Stress and Inflammation in Cancer Theories of Cancer Development Mind-body techniques * Yoga Mindfulness * Cognitive / Behavioral therapy Meditation * Energy-Based Techniques Reiki * Acupuncture Acupressure * Meridian tapping Natural Products * Vitamins and minerals Botanicals * Fish Oils Probiotics * Exercise Walking * Swimming / Hiking Bicycling * Zumba / Dance Fitness Source: Payne, J.K. (2014). State of the Science: Stress, Inflammation, and Cancer. Oncology Nursing Forum, 41(5), Genetic Influences Associated with Cancer Genetic Mutations 5

6 Cancer Genetics Hereditary Breast & Ovarian Cancer Syndromes Hereditary Nonpolyposis Colorectal Cancer Syndrome (HNPCC) Autosomal dominant syndrome accounts for 3%-5% of all colorectal cancers Familial Adenomatous Polyposis Syndromes (FAP) Risk of developing colorectal cancer is virtually 100% Associated with endometrial, ovarian, gastric, bile duct, small bowel, renal pelvis, and ureter cancers Four mutations in the genes MSH2, MLH1, PMS2, and MSH6 have been associated Age at onset can occur before age 20 Screening with colonoscopy and upper endoscopy at puberty Colectomy when symptomatic or when number of adenomas is not manageable with polypectomy 6

7 Genetic Mutations Angiogenesis Angiogenesis The Metastatic Process 7

8 The Metastatic Process The Metastatic Process Overall most common sites of metastases Bone Brain Liver Lungs Lymph nodes 8

9 Pathologic Diagnosis of Cancer Pathologic Diagnosis of Cancer 9

10 Grading and Differentiation Grade: Degree to which the tumor cells resemble parent tissue Tumor Grade GX G1 G2 G3 G4 Grade can not be assessed Well-differentiated (Low grade) Moderately-differentiated Poorly-differentiated Undifferentiated (High grade) α-fetoprotein Diagnostic Biomarkers for Staging and Monitoring Human chorionic gonadotropin-β CA 19-9: CA 125: CEA CA 15-3, CA 27-29, HER2/NEU Fibrin / FDP, BTA, High molecular weight CEA & mucin, chromosomes 3, 7, 9, 17 Thyroglobulin PSA Testicular cancer (nonseminatous) Testicular cancer Pancreatic cancer Ovarian cancer Colon cancer Breast cancer Bladder cancer Thyroid cancer Prostate cancer Four Different Types of Staging Clinical Staging determines how much cancer there is based on physical exam, imaging tests, & biopsies of affected areas. Pathologic Staging only determined from individual patients who ve had surgery to remove a tumor or explore extent of the cancer. Pathologic staging combines results of clinical staging (physical exam, imaging test) & surgical results. Post-Therapy or Post-Neoadjuvant Therapy Staging determines how much cancer remains after patient is 1st treated with systemic (chemo or hormone therapy) and/or radiation therapy prior to surgery or where no surgery is done. Assessed by clinical and/or pathologic staging guidelines. Restaging is used to determine the extent of the disease if a cancer comes back after treatment. Restaging helps determine the and the best treatment options for cancer that has returned. 10

11 Common Elements of Staging Staging is based on commonly understood knowledge about the way cancer develops and spreads. In most cases, the stage is based on four main factors: Location of the primary (original) tumor Tumor size and extent of tumors T = TUMOR N = NODES TMN Staging Local involvement, invasion e.g. extent of primary tumor Lymph node involvement, e.g. presence / absence of regional lymph node metastases Lymph node involvement (whether or not the cancer has spread to the nearby lymph nodes) Presence or absence of distant metastasis (whether or not the cancer has spread to distant areas of the body) M = METASTASIS Distant location(s), e.g. presence or absence of distant metastases TNM System TNM System 11

12 TMN System Typical TNM Staging TMN Staging for Lung Cancer 12

13 TMN Staging for Lung Cancer TMN Staging for Lung Cancer Other Classification Systems Questions? Cotswald Classification World Health Organization (WHO) Lung Cancer: SCLC versus NSCLC 13