Neoplasia

Dr.  Romeo  P.  Mostoles,  Jr.  

Assistant  Professor,  College  of  Nursing  
Coordinator,  Nursing  Review  Program  
University  of  Hail  
 Neoplasia

•  Means “new growth”

•  Implies abnormality of cellular growth/tumor
•  Malignant neoplasm iscancer
•  Benign growth is generally easily cured
•  Malignant cancer may not be survivable
•  Cancer is associated with altered expression
of cellular genes
BENIGN  VS.  M A L I G N A N T  G ROWTH  

Malignant Tumor
•  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
BENIGN  VS.  M A L I G N A N T  G ROWTH    
(CONT.)  
BENIGN  VS.  M A L I G N A N T  G ROWTH    
(CONT.)  
Benign Tumor
•  Does not have potential to kill host, but may
be life-threatening because of its location
•  Does not invade adjacent tissue or spread to
distant sites
•  Many are encapsulated
•  More closely resembles original tissue type
•  Grows more slowly, little vascularity, rarely
necrotic, often retains original function
BENIGN  VS.  M A L I G N A N T  G ROWTH    
(CONT.)  
Benign Tumor
•  “-oma” suffix indicates benign tumor
(adenoma)
•  “-carcinoma,” “-sarcoma” indicate
malignant tumors
•  Carcinoma: malignant tumor of epithelial
origin (adenocarcinoma)
•  Sarcoma: malignant tumor of mesenchymal
origin
•  Leukemia: malignant growth of white blood
cells
 EPIDEMIOLOGY  A N D  C A N C E R    
RISK  F ACTORS  
•  Cancer is 2nd leading cause of death in the
U.S.
•  Most cancer deaths occur in individuals over
age 55
•  Men have 1:2 risk of developing cancer;
women have 1:3risk
•  5-year survival rate: 66%
EPIDEMIOLOGY  A N D  C A N C E R    
RISK   F ACTORS  ( CONT.)  
EPIDEMIOLOGY  A N D  C A N C E R    
RISK  FACTORS  ( CONT.)  
•  One third of cancer-related deaths may be
attributable to lifestyle factors
•  Tobacco use
•  Nutrition
•  Obesity
•  Sun exposure (skin cancer)
•  Sexual exposure to HPV (cervical cancer)
•  Early screening aids in early detection
 T O B A C C O  U SE  

•  Death rate from lung cancer has dramatically

increased (may be directly related to
smoking)
•  Lung cancer: leading cause of death in men
and women; worst survival rate
•  Also linked to pancreatic, kidney, bladder,
mouth, esophageal, and cervical cancers
T O B A C C O   USE  ( CONT.)  
 T O B A C C O   USE  ( CONT.)  

•  Two types of carcinogens

•  Initiator (causes genetic damage)
•  Promoter (promotes tumor growth)
•  Tobacco smoke contains both types
•  Second-hand smoke also increases risk for
lung cancer
T O B A C C O   USE  ( CONT.)  
 N UTRITION  

•  Dietary factors believed to be related to

cancer risk
•  Fat
•  Fiber
•  Alcohol
•  Antioxidants
 GENETIC  MECHANISMS  O F    
C A N C E R  
•  Carcinogen
•  Potential cancer-causing agent
•  Proto-oncogene
•  Overactivity of cancer-critical genes contributes to
cancer
•  Oncogene
•  Proto-oncogene in its mutant overexpressed form
•  Tumor suppressor gene
•  Too little gene activity; inhibits cell proliferation
•  Cancers may arise when tumor suppressor gene
function is lost or abnormally inhibited
 PRO TO -­‐O N C O G EN ES  

•  Normal cellular genes that can be

transformed into oncogenes by activating
(gain-of-function) mutations
•  Code for
•  Growth factors
•  Receptors
•  Cytoplasmic signaling molecules
•  Nuclear transcription factors
PROTO-­‐ONCOGENES  ( CONT.)  
GROWTH  FACTORS  ( MITOGENS)  

Small Cell−Manufactured Peptides

•  Secrete into extracellular space
•  Diffuse to nearby cells
•  Interact with receptors on target cell surface
•  Activate signaling cascade; can produce
autocrine signaling
GROWTH  FACTOR  R ECEPTORS  

•  Transmembrane proteins
•  Mitogen-binding area on outside of cell
•  Enzyme-activating area on inside of cell
•  Will bind with only one particular mitogen
•  Binding activates cell proliferation
 CYTOPLASMIC  S IGNALING  
PATHWAYS  
•  Involve numerous enzymes and chemicals
that normally function to transmit signals from
activated receptors at cell surface to cell
nucleus
•  Mutant proto-oncogene can activate
pathway, even when no signal received at
cell surface
 TRANSCRIPTION  F ACTORS  

•  Proteins that must be assembled at the

promoter area to begin gene transcription
•  Normally sequestered and prevented from
indiscriminate activity until appropriate signals
cause their release
•  Mutations may cause overproduction of
transcription factors
FROM  PROTO-­‐ONCOGENE  T O    
O N C O G E N E  
•  Proto-oncogenes become activated
oncogenes when mutations alter their
activity so that proliferation-promoting
signals are generated inappropriately
•  Oncogenes introduced to host cell by retrovirus
•  Proto-oncogene within cell suffers a mutagenic
event
•  DNA sequence may be lost/damaged and
allows proto-oncogene to become abnormally
active
•  Error in chromosome replication causes extra
copies of proto-oncogene in the genome
FROM  PROTO-­‐ONCOGENE  T O    
O N C O G E N E  ( CONT.)  
FROM  PROTO-­‐ONCOGENE  T O    
O N C O G E N E  ( CONT.)  
•  Retrovirus
•  HIV
•  Kaposi’s sarcoma
•  Epstein-Barr virus
•  Burkitt lymphoma
•  Human T-lymphocyte virus type 1
•  Adult T-cell leukemia/lymphoma
•  Composed of RNA
•  Contains reverse transcriptase enzyme
•  Directs synthesis of a DNA copy of viral RNA
FROM  PROTO-­‐ONCOGENE  T O    
O N C O G E N E   TRANSCRIPTION    
FACTORS  
 TUMOR-­‐SUPPRESSOR  G ENES  

•  Contribute to cancer only when not present

•  Both copies of tumor suppressor genes are
inactivated when cancer develops
•  One can inherit a defective copy of tumor
suppressor gene from 1 or both parents
TUMOR-­‐SUPPRESSOR  G ENES    
(CONT.)  
 RB  G ENE  

•  Codes for large protein in cell nucleus

(pRb) that is the “master break” for the
cell cycle
•  Blocks cell division
•  Binding transcription factors
•  Inhibits Tfactors from transcribing genes that
initiate cell cycle
•  Can be induced to release transcription
factors when sufficiently phosphorylated
•  An inactivating mutation of the Rb gene
removes 1 major restraint on cell division
RB  G ENE  ( CONT.)  
 P53  G ENE  

•  Most common tumor-suppressor gene defect

identified in cancer cells
•  More than ½ of all types of human tumors lack
functional p53
•  Inhibits cell cycling
•  Accumulates only after cellular (DNA)
damage
•  Binds to damaged DNA and stalls division
P53  G ENE  (CONT.)  
 P53  G ENE  (CONT.)  

•  May direct cell to initiate apoptosis

•  Allows genetically damaged/unstable cells to
survive and continue to replicate
•  Chemotherapy/radiation
•  Damages target cell to trigger p53-mediated cell
death
•  Cancer cells that lack functional p53 may be
resistant to chemotherapy/radiation
 BRCA1  A N D   BRCA2  G ENES  

•  Breast cancer genes

•  Family history and inherited defect in BRCA1
increases risk of breast and ovarian cancer
BRCA1  A N D   BRCA2  G ENES    
(CONT.)  
 MULTISTEP  NATURE  O F    
CARCINOGENESIS  
•  Initiation
•  Promotion
•  Progression
 MULTISTEP  NATURE  OF    
CARCINOGENESIS  ( CONT.)  
 MULTISTEP NATURE OF
CARCINOGENESIS (CONT.)
 INITIATION

•  Initiating events
•  Genetic mutations
•  Inappropriately activate proto-oncogenes
•  Inactivate tumor suppressor genes
•  Proliferation
•  Required for cancer development (nonproliferating
cells cannot cause cancer)
•  Each type of cancer has its own combination
of mutations that lead to malignancy
INITIATION (CONT.)
 INITIATION (CONT.)

•  Complete carcinogens
•  Capable of initiating cell damage as well as
promoting cellular proliferation
•  Partial carcinogens
•  Promoters that stimulate growth
•  Incapable of causing genetic mutations sufficient to
singly initiate cancer
 PROMOTION

•  Stage during which mutant cell proliferates

•  Activation of another oncogene
•  Inactivation of tumor suppressor gene
•  Nutritional factors
•  Infection
•  Regulated by many hormonal growth factors
(hormones may be promoters for certain
cancers)
•  Estrogen
•  Testosterone
 PROGRESSION

•  Mutant, proliferating cells begin to exhibit

malignant behavior
•  Malignant cells commonly produce
telomerase (an enzyme that repairs telomeres
and may be a key for attaining immortality)
•  Cells whose phenotype gives them a growth
advantage proliferate more readily
•  Requires multiple steps
PROGRESSION (CONT.)
 METASTASIS

•  Process by which cancer cells escape their

tissue of origin and initiate new colonies of
cancer in distant sites
•  Specialized enzymes and receptors enable them to
escape their tissue of origin and metastasize
METASTASIS (CONT.)
 PATTERNS OF SPREAD

•  Cancer cells generally spread via circulatory

or lymphatic systems
•  Tumor markers help identify parent tissue of
cancer origin
•  Rely on some retention of parent tumor
characteristics
•  Some released into circulation
•  Others identified through biopsy
•  Enzymes typically used as tumor markers
•  Help track tumor activity
 ANGIOGENESIS

•  Process by which cancer tumor forms new

blood vessels in order to grow
•  Usually does not develop until late stages of
development
•  Triggers are not generally understood
•  Inhibition of angiogenesis isimportant
therapeutic goal
 GRADING AND STAGING OF
TUMORS
•  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
 GRADING AND STAGING OF
TUMORS (CONT.)
•  Staging
•  Location and patterns of spread within the host
•  Tumor size, extent of local growth, lymph node and
organ involvement, distant metastasis
•  TNM system most widely used
•  Results of staging determine treatment
modality
GRADING AND STAGING OF
TUMORS
 EFFECTS OF CANCER ON THE
BODY
•  Depends on location of tumor and extent of
metastasis
•  Early stages may be symptomatic
•  Tumor increases in size and spreads; more
symptoms become apparent
EFFECTS OF CANCER ON THE
BODY (CONT.)
 WARNING SIGNS OF CANCER

•  Change in bowel or bladder habits

•  A sore that does not heal
•  Unusual bleeding or discharge
•  Thickening or lump in breast or elsewhere
•  Indigestion or difficulty swallowing
•  Obvious change in wart or mole
•  Nagging cough or hoarseness
WARNING SIGNS OF CANCER
IN CHILDREN
•  Continued, unexplained weight loss
•  Headaches with vomiting in the morning
•  Increased swelling or persistent pain in bones
or joints
•  Lump or mass in abdomen, neck, or
elsewhere
•  Development of whitish appearance in pupil
of the eye
•  Recurrent fevers not caused by infections
•  Excessive bleeding or bruising
•  Noticeable paleness or prolonged tiredness
 PA I N  

•  Common and feared complication

•  May be due to metastasis, tissue
destruction/inflammation
•  May be caused by cancer treatment
•  Usually controlled with analgesics
 C A C H E X I A   A N D  I MMUNE    
SYSTEM  D EFICITS  
•  Cachexia
•  Overall weight loss and generalized weakness
•  Loss of appetite (anorexia)
•  Increased metabolic rate
•  Nausea/vomiting
•  Immune system suppressed by cancer cell
secretions
•  Some cancers can elude immune system
detection
BONE  MARROW  S UPPRESSION  

•  Contributes to anemia, leukopenia, and

thrombocytopenia
•  Due to invasion and destruction of bone
marrow cells, poor nutrition, and
chemotherapy
•  Anemia: Deficiency in circulating red blood
cells
 LEUKOPENIA  

•  Deficiency in circulating white blood cells

•  Primary cause
•  Malignant invasion of bone marrow
•  Contributing factors
•  Malnutrition
•  Chemotherapy
•  Opportunistic organisms can only infect
immunocompromised host
•  Infections difficult to manage, prevent
 THROMBOCYTOPENIA  

•  Deficiency in circulating platelets

•  Important mediators in blood clotting
•  Predispose to life-threatening hemorrhage
•  Anemia, leukopenia, thrombocytopenia can
all be managed by blood replacement
therapy
 OTHER  E FFECTS  

•  Hair loss and mucositis

•  Complications of chemotherapy and radiation
therapy
•  Mucositis primary source of cancer pain and anorexia
•  May provide a portal for infection
•  Paraneoplastic syndromes
•  Hypercalcemia
•  Cushing syndrome secondary to ACTH secretion
•  Hyponatremia and water overload secondary to
excess ADH secretion
 C A N C E R  T HERAPY  

•  Early detection best prognosis for cure

•  Mainstays of therapy
•  Surgery
•  Radiation therapy
•  Chemotherapy
•  Drug therapy
•  Emerging therapies
•  Immunotherapy
•  Targeted molecular therapies
•  Stem cell transplantation
C A N C E R   THERAPY  ( CONT.)  
 SU RG ERY  

•  Majority of patients with solid tumors are

treated surgically
•  Main benefit: removal of tumor with minimal
damage to other body cells
•  Lymph nodes biopsied and/or removed
•  Commonly accompanied by radiation
therapy or chemotherapy
 RADIATION  T HERAPY  

•  Kills tumor cells by damaging nuclear DNA

•  Kills cells that are nonresectable due to
location, missed by surgery, or undetected
•  May not kill cells directly, but initiates
apoptosis
•  Small doses of radiation over several
treatments (difficult to kill at once because
cells on different cycles)
•  Some normal cells killed during radiation
therapy
 D R U G  T HERAPY  
•  Systemic administration of anticancer
chemicals to treat cancers known or
suspected to be disseminated in the body
•  Finds cancer cell targets in the body
•  Most are cytotoxic
•  Not selective for tumor cells (normal cell
death may also occur)
 D R U G   THERAPY  ( CONT.)  
•  Most effective on rapidly dividing cells
•  Several courses ensure all cancer cells killed
•  Serious side effect: bone marrow suppression
 IMMUNOTHERAPY  

•  Primarily involves use of:

•  Interferons
•  Glycoproteins produced by immune cells in response to
viral infection
•  Interleukins
•  Peptides produced and secreted by white blood cells
•  Monoclonal antibodies
•  Antibodies with identical structure that bind with
specific target antigens
•  Generally used as adjuncts to surgery,
irradiation, and chemotherapy
 GENE  A N D  M O L E C U L A R    
THERAPY  
•  May have high therapeutic potential
•  May be used to suppress overactive
oncogenes or replenish missing tumor
suppressor function
•  Current uses
•  Genetic alteration of tumor cells to make them
more susceptible to cytotoxic agents or immune
recognition
•  Genetic alteration of immune cells to make them
more efficient killers of tumor cells
•  Can be directed at cells other than cancer
cells
STEM  CELL  T RANSPLANTATION  

•  Used to manage life-threatening disorders in

which patient’s bone marrow cannot
manufacture white blood cells, red blood
cells, or platelets
•  Also applied to other malignancies and to
nonmalignant disorders
•  Provides a method to restore bone marrow
function after high-dose irradiation or
chemotherapy