Non-targeted Cancer Therapies Flashcards
What are prevention strategies in Cancer?
= better to prevent than treat
(many cancers are in theory preventable)
BUT cancer still prevalent because:
= many prevention strategies rely on personal choices
= many cancers occur at random and are not preventable
What are the traditional cancer therapies?
Surgery
= resection of tumour
Radiotherapy
= induce cell death by irradiation
Chemotherapy
= induce cell death using chemical agents
What is surgical oncology?
= good choice for many primary tumours
= only curative if not metastatic
= commonly used in combined therapy
= e.g. early stage colorectal cancer (95% 5 year survival)
= preventative measure in cases of inherited mutations
(e.g. FAP - removal of large intestine, BRCA - mastectomy)
= draining lymph nodes can also be removed
= some metastsases can be removed by surgery but this is often impractical
= aim is to remove all cancerous tissue (+ small healthy margin)
= can use Fluorescence-guided surgery to visualise tumour better
What are the types of Radiotherapy?
- External beam therapy
(source from outside of body) - Brachytherapy
(material adjacent to tumour cell) - System
(liquid by mouth or injected intravenously)
= can be used alone BUT often in combination with other therapies (e.g. surgery)
= can be used before (neoadjuvant) or after surgery (adjuvant) = dependent on cancer type
= damages normal as well as cancer cells
(BUT cancer cells are more sensitive as they are dividing more rapidly and may have mutations in DNA repair pathway)
What are the types of External Beam Therapy? (Radiotherapy)
- X-rays or gamma rays (= photon radiotherapy)
= directly ionises DNA
= induces free radicals
= induction of DNA Damage Response (DDR)
= either cell cycle arrest and DNA repair
= OR apoptosis - Proton-beam therapy
= high energy positively charged particles
= causes direct and indirect DNA damage
= have more advantages but technically difficult
= suitable only for a few cancers e.g. Uveal Melanoma
Dose delivery is different
= photons peak and then slowly decreases = affects surrounding tissue a lot
= protons are targeted directly on tumour = Bragg peak - deposits all energy = less damage to surrounding tissue
What is an example of Brachytherapy? (Radiotherapy)
= e.g. to treat uveal melanoma
= small radioactive source placed inside or next to tumour
(e.g. radioactive seeds = iodine-125 or ruthenium-106)
= radiation emitted damages cancer cells
EXTRA READING
= radioactive source usually delivered through a catheter or applicator
= can treat prostate, breast, cervical and skin cancers also
= type / duration of treatment depends on cancer type / stage
What is Systemic Therapy? (Radiotherapy)
Radiopharmaceuticals
= liquid drug
= taken by mouth or injection
= radioactive isotope (e.g. iodine, strontium, samarium and radium)
= can be coupled to a monoclonal antibody to direct drug to tumour
= e.g. of cancer treated = thyroid, bone and prostate
How does resistance to radiotherapy occur?
Tissue specific gene expression
= deficient DNA repair mechanisms
= e.g. p53, ataxia telangiectasia mutated (ATM) status
Solid tumours often HYPOXIC environment / patient often anaemic
= failure to induce free radicals
What are some strategies to improve radiation therapy?
Increase intratumoral oxygenation
= increase perfusion with vasoactive agents to enhance blood flow
Sophisticated treatment planning + delivery
= 3D conformal radiation therapy
= intensity-modulated radiation therapy
= stereotactic radiation therapy / radiosurgery
= brachytherapy (inside or next to tumour)
Alternative radiation regimes
= high-energy transfer radiation
= new fractionation regimes
= combined-modality regimes
Alternative radiation types
= high energy proton beam therapy
= heavy ions such as carbon (still experimental)
What is ‘Traditional’ Chemotherapy?
Most agents disrupt cell proliferation
= most effective against rapidly dividing cells
= efficacy depends on amount of drug reaching the tumour and its residence time
= non-specific, therefore = side effects
Therapeutic index (TI)
= difference between the minimum effective dose and the maximum tolerated dose
= higher the TI = fewer side effects
When is Chemotherapy Used?
Neoadjuvant chemotherapy
= to shrink a tumour before surgery or radiation to improve chances surgery / radiation will be effective
Adjuvant chemotherapy
= post surgery = to kill any remaining cells
Curative chemotherapy
= as a single therapy to cure cancer
= e.g. leukemia and lymphoma
Palliative chemotherapy
= for patients with advanced / metastatic cancer goal may be to delay cancer growth and to help manage symptoms
How do chemotherapies disrupt cell proliferation?
Most affect cell cycle
= so will also affect normal cells
Targeted treatments use genetic information from patients to target oncogenic features of the cells
= target cancer mutations specific to those cells
Target rapidly diving cells
1. Antimetabolites
= interfere with DNA-synthesis (S-phase)
- Anthracyclines
= intercalate into DNA (S/G2 phases) - Microtubule binders
= M phase - Alkylating agents
= damage DNA (all phases but especially S) - Differentiation
= forcing cells to exit cell cycle (G0)
What are some side effects of Chemotherapy?
Many due to normal, rapidly diving cells being effected
= e.g. may result of compromised renewal of epithelial barrier
also
= hair loss
= pain
= mouth sores
= trouble breathing
= nausea / vomiting
= weakened immune system
= bruising bleeding
= rashes
= neuropathy
How is Chemotherapy administered?
Some are an oral pill
= but most are given intravenously
e.g. Initial treatment for lung cancer
= usually involves the use of 2 or more drugs
(combination chemotherapy)
= these drugs often given in cycles of 3-4 weeks at least 4-6 times
What are Anti-metabolites (Chemotherapy)?
= interfere with DNA-synthesis (S-phase)
= similar to naturally occurring compounds
= interfere with DNA synthesis
(inhibit nucleic acid synthesis, S-phase specific)
= require active transport
= breast cancer, leukaemia, lung cancer
= e.g. MTX (methotrexate), 5-FU (5-fluorouracil)
MTX
= analogue of folic acid
= inhibits enzyme dihydrofolate reductase
= blocks purine and pyrimidine nucleic acid synthesis
(inhibiting DNA and RNA synthesis)
= blocks in S phase
What is combination chemotherapy?
= minimise side effects
= circumvent problems with drug resistance
