Cancer therapy strategies - Standard therapies Flashcards
Cancer therapy types
- hormone therapy
- surgery
- bone marrow transplantation
- chemotherapy
- targeted therapy
- radiation therapy
- immunotherapy
Surgery in cancer treatment -> prevent cancer
- Preventive or prophylactic surgery is used to minimize the risk of developing certain types of cancer
- Removal of precancerous conditions, that make them more likely to develop into cancer
- Removal of atypical moles to prevent skin cancer
- Removal of polyps to prevent colon cancer
- Removal of breast tissue and ovaries in patients with BRCA1 or BRCA2 mutations
ABCDEs of melanoma:
- asymmetry (irregular shape)
- border (irregular border)
- color (multiple colors)
- diameter (>6mm in diameter)
- evolving (change in size, shape or color)
Surgery in cancer treatment -> diagnose and stage cancer
Surgery can be performed to collect biopsy samples from the tumor or sentinel lymph nodes
-> incisional biopsy – part of the tumor is cut out
-> excisional biopsy – the entire tumor is cut out. A margin of healthy tissue is usually removed at the same time
Evaluation of cancer type and metastatic state can influence the treatment strategy
Surgery in cancer treatment -> remove cancer
- completely remove the tumor or cancerous tissue
- most effective at an early stage in cancer development
- avoid the cut through the tumor to minimize cancer cells scattered and spread to other structures
- surgical margin: area around the tumor which consist of normal tissue
Surgery in cancer treatment -> relieve symptoms
Palliative surgery is used to relieve symptoms and improve the quality of life
- evaluation of the extent of the disease
- control of loco-regional spread
- control of discharge or hemorrhage
- control of pain
- surgical reconstruction or rehabilitation
Risk-benefit evaluation is necessary
Surgery in cancer treatment -> lower the chance of recurrence
- Radical surgery: remove other nearby normal structures including muscles, nerves and lymph nodes
- e.g. radical mastectomy removes all of the breast along with chest muscles and lymph nodes under the arm
- Can minimize cancer recurrence
Surgery in cancer treatment -> Repair damaged tissue
- Surgery is used to repair tissue that is damaged by cancer or cancer treatments
- Reconstructive: medically indicated
- Cosmetic: rebuild the body shape
Surgery in cancer treatment -> Support other treatments
- Provide direct access to blood vessels (e.g. by a central venous catheter)
- place a special pump that is used to deliver chemotherapy drugs
Surgery in cancer treatment -> Support body function
- Surgeries that help with body functions such as breathing and getting enough nutrition
- Examples: tracheostomy or gastrostomy
Radiation therapy
- Ionizing radiation carries sufficient energy to detach electrons from atoms or molecules, thereby ionizing them
How penetrating?
- paper: stops alpha rays
- thin aluminium: stops beta rays
- thick lead: stops gamma, X rays
- water or concrete: stops neutron rays
EXTERNAL BEAM RADIATION THERAPY
* Therapy using ionizing radiation delivered by a linear accelerator
* Temporary
* High speed particles collide with a target inside the machine
* Photons are released and targeted to the patient
* Electrons and protons are alternative types of radiation, but less commonly used
INTERNAL RADIATION THERAPY
* Brachytherapy: Seeds that contain a radiation source are placed near the tumor
* Temporary or permanent
* Systemic radiation therapy: radioactive drugs that circulate through the body
* Examples: iodine-131, radium-223
How does radiation damage cancer cells
-> Ionizing radiation works by damaging DNA of cells leading to cellular death
INDIRECT
- Radiation hits water molecules and other organic molecules in the cell
➜ production of free radicals like hydroxyl (HO) and superoxide (O2–)
- Short lived and rapidly interact with biomolecules
- Most important ROS are generated in 2 nm distance from DNA
DIRECT
- Less common
- Heavier particles like protons rely on direct DNA damage
Hypoxia leads to radiation therapy resistance ➜ less formation of radicals like superoxide
- Direct and indirect DNA damage by radiation causes single and double strand breaks
- Double-stranded DNA breaks are much more difficult to repair increasing the probability that cells will undergo cell death
- Dividing cells are more sensitive to radiation therapy than differentiated normal tissue
- Cancer cells are more sensitive in G2/M phases of the cell cycle than in G1/S
- Total dose of radiation is fractionated
- Fractionation regimens are individualized between different radiation therapy centers and even between individual oncologists
- Typical fractionation schedule for adults is 1.8 to 2 Gy per day, five days a week
Fractionation of radiation therapy
- Fractionation is based on the “4R”-principle: biological factors influencing the response of a tumor and normal tissues
REPAIR (few hours)
* normal cells recover, less time for repair in tumor cells leads ➜ error-prone
REASSORTMENT/REDISTRIBUTION (few hours)
* tumor cells that are in a relatively radio-resistant phase cycle into a sensitive phase
of the cell cycle before the next fraction is given
REPOPULATION (5-7 weeks)
* Increase in cell division
* Effective suppression of tumor cell repopulation
* Accelerated repopulation (rapid multiplication of surviving clonogens) may contribute to local failure
REOXYGENATION (hours to few days)
* Tumor cells that are hypoxic are more radio-resistant
* Reoxygenation between fractions, improving tumor cell death
Side effects
- Radiation therapy is painless
- Side effects from radiation are usually limited to the area of the patient’s body that is
under treatment
ACUTE
- Akin reddening
- fatigue
- delayed wound healing
- hair loss in treatment area
- muscle aches
CHRONIC
- swelling
- skin thickening
- joint stiffness
Rare:
- bone fractures
- sterility
- secondary tumors
Goals of chemotherapy
Chemotherapy in the treatment of cancer can have different goals
- curative chemotherapy: aims to eliminate all cancer cells from the body to achieve a permanent cure
- palliative chemotherapy: to relive certain symptoms, to slow down the progress of the disease or to stop it temporarily
- neoadjuvant chemotherapy: is done before surgery to shrink the tumor size and to allow less invasive surgery
- adjuvant chemotherapy: aims at cancer cells that might be left in the body after surgery and is performed to prevent recurrences
Chemotherapy - mechanisms
G1 CHECKS FOR:
- cell size
- nutrients
- growth factors
- DNA damage
G2 CHECKS FOR:
- cell size
- DNA replication completeness
M CHECKS FOR:
- spindle checkout
- specific complexes of cyclin and cyclin-dependent kinases are formed and activated at different phases of the cell cycle
