Top 3 cancer in the US:
Incidence:
1) Prostate or Breast
2) Lung
3) Colorectal
Mortality:
1) Lung
2) Prostate or breast
3) Colorectal
Environmental factors that cause cancer:
Smoking
Radiation
Obesity
Several Oncogenic viruses
Helicobacter pylori
Clinical Manifestations of Cancer
Pain
Fatigue
Cachexia
Anemia
Leukopenia & thrombocytopenia
Infection
Hair loss & sloughing of mucosal membranes
Paraneoplastic Syndromes
Pain
Pain is a subjective clinical manifestation.
Pain occurs in 60% - 80% of terminally ill patients
Pain is strongly influenced by stressors such as: fear, anxiety, fatigue, lack of sleep, and overall physical deterioration.
General mechanisms that cause cancer-associated pain include:
- Pressure of the growing tumor
- Obstruction of blood vessel causes nearby tissues to necrosis
- invasion of a sensitive structure
- stretching of visceral surfaces
- tissue destruction
- inflammation
Fatigue
Fatigue is a subjective clinical manifestation.
Fatigue is the most frequently reported symptom of cancer and its treatment.
Fatigue is described by cancer patients as: tiredness, weakness, exhaustion, inability to concentrate, depression, sleepiness, & l
General mechanisms that cause fatigue include:
1) sleep disturbances
2) biochemical changes secondary to disease & treatment (anemia)
3) psychosocial factors
4) level of activity (lack of exercise)
5) nutritional status
Cachexia
Cachexia is a syndrome that includes:
1) anorexia (lack of appetite)
2) early satiety (filling)
3) weight loss
4) anemia
5) asthenia (marked weakness)
6) poor performance
7) taste alterations (metallic taste)
8) altered protein, lipid, and CHO metabolism
anorexia-cachexia syndrome
is present in 80% of cancer patients at death (and pain)
The anorexia-cachexia syndrome is one of the most common causes of death in cancer patients.
Proinflammatory cytokines play a major role in the development of cachexia:
TNF-alpha
IL-1
IL-6
Interferon gamma
Anemia caused by:
chronic bleeding (results in iron deficiency)
severe malnutrition
medical therapies
malignancy in blood-forming organs
EPO
erythropoietin. is effective in the treatment of anemia
SAS of anemia include
fatigue
increased heart rate
increased respiratory rate
The 2 most common causes of leukopenia and thrombocytopenia are:
Direct tumor invasion of the bone marrow
Bone marrow suppression due to chemo or radiation
Thrombocytopenia is the major cause of
bleeding in cancer patients
Infection
Infection is the most significant cause of complications and death in cancer patients.
The main factors that decreases a patient's resistance to infection include:
1) leukopenia
2) immunosuppression from radiotherapy & chemotherapy (target the rapidly dividing cells)
3) debility with advanced disease
4) surgery creating favorable sites for infection
5) nosocomial infections increase
Paraneoplastic syndromes
10% of individuals with cancer are affected
Common paraneoplastic syndromes include
Cushing syndrome 2o to excess ACTH secretion
Hyponatremia and water overload 2o to excess ADH
Hypercalcemia associated with abnormal production of parathyroid hormone-related protein by tumor cells
Unexplained hypercalcemia
is regarded as evidence of cancer until proven otherwise
Cancer's 7 warning signs (CAUTION)
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
3 primary causes of cancer death are:
1) Injection due to immunosuppression
2) Hemorrhage
3) Organ failure
Cancer treatment challenge
Cancer therapies can successfully eradicate the primary tumors
The challenge is controlling metastasis
Current overall 5-year survival rate for patients with cancer is
about 66%
Cancer is treated with :
Chemotherapy
Radiotherapy
Surgery
Hormonal therapy
Immunotherapy
Combination therapy
Gene therapy
Stem cell replacement
Chemotherapy
is the systemic administration of relatively nonselective cytotoxic drugs that target vital cellular machinery/metabolic pathways critical to both malignant and normal cell growth and replication
To be curative, chemotherapy must
eradicate enough tumor cells so that the body's own defenses can wipe out any remaining cells.
The primary rationale for combination chemotherapy is to
avoid single-agent drug resistance, which may be present even in previously-untreated tumors.
Adjuvant chemotherapy
after local treatment or after removal of primary tumor
Neoadjuvant
Early use of agents before definitive local control to decrease initial tumor size
Several course of chemotherapy is to:
Ensure that all tumor cells have been killed since at any give time, only a portion of the tumor cells are in a cell-cycle stage susceptible to chemotherapy
Normal Cells that's being affected under chemo are:
Bone marrow, hair follicles, GI muscosa
Side effects of chemo and radiotherapy include:
Anemia
Hair loss
Nausea
Infection
Pain
TI
Therapeutic index = max tolerated dose / lowest curative dose
Radiotherapy
Effective for cancers that are localized.
Killed cell by damaging nuclear DNA and initiating apoptosis
Goals of ionizing radiation are:
1) To eradicate cancer without producing excessive toxicity during treatment.
2) To avoid damage to normal structures.
Radiation may cause the following types of damage:
1) lethal (cell is killed)
2) potentially lethal (cell will die)
3) sublethal (cell is damaged but can repair itself)
Surgery is effective when
Cancers are localized
Surgical therapy has several objectives:
1) Surgical biopsy begins the treatment process. (grading)
2) Curative resections are performed if distant metastasis is not evident.
3) Debulking surgery. If the tumor cannot be completely excised, debulking surgery is performed to remove the majority of
Immunotherapy
Has the potential to specifically target cancer cells
Adoptive immunotherapy
is a technique for artificially improving cell-mediated immunity by one of the two mechanisms:
1) Increasing the number of specific immunocompetent cells
2) Altering tumor cells to make them more immunogenic
BRM
Biological response modifiers comprise a group of products intrinsic to the body that alter immune/inflammatory defenses to enhance, direct or restore the body's ability to fight disease
BRM operate via one or more of the following mechanisms:
1) BRMs have a direct cytotoxic effect on cancer cells
2) BRMs initiate or augment the host's tumor-immune rejection response
3) BRMs modify cancer-cell susceptibility to the lytic or tumor-static effects of the immune system
Five representative BRMs are:
1) Immunomodulating agents
2) Inteferon
3) Antigens
4) Effector cells and lymphokines
5) Monoclonal antibodies
Gene therapy
1) Generic alteration of tumor cells to make them more susceptible to (a) cytotoxic agents and (b) immune recognition.
2) Genetic alteration of immune cells to make them more efficient killers of tumor cells.
Stem cell transplantation
Restore bone marrow function after high-dose irradiation or chemotherapy.
Antibodies battle cancer via 2 mechanisms:
1) Cytotoxic antibodies activate complement-killing of tumor cells
2) Noncytotoxic antibodies use a mechanism called ADCC (K cells bing and deliver a tumor-killing signal)