Unit 09 Cancer background Flashcards
What are the classes of anticancer drugs
- Acts on DNA
- Damanges DNA
- Alkylating agents
- free radicals/intercalating agents
- Inhibit synthesis
- Antimetabolites
- Damanges DNA
- Inhibits chromatin function
- Topoisomerase inhibitors
- microtubule inhibitors
- Acts on hormone.steroid receptors
- Agonist
- antagonist
what is malignant neoplasm
name for cancer
- cells grow uncontrollably, invade surrounding tissue and sometimes colonize other locations in the body (metastasis)
what is angiogenesis
growth of new blood vessels from existing vasculature
-critical part of tumor growth bc allows new abnormal cells to cont to grow by providing oxygen and nutrients
how to tumors induce blood vessel growth
secret growth factors
- blood vessel growth also related to metastasis (colonization of other locations in body) - cells move away from primary tumor and invade other parts of body through blood or lymph
what is the most feared and least understood aspect of cancer?
Metastasis
- patients suffering from cancer will die from secondary disease, not the original tumor
- occurs when cells detach from parent tumor and enter blood or lymph vessel, exit from ciruclation and proliferation in the new environment
What is a carcinoma?
- cancers of epithelial cells lining surface of organs
what are sarcomas
cancers of muscle, bone, cartilage, fat or connective tissue
what is leukemia?
cancer of white blood cell or blood precuror cells
what is lymphoma
cancer of bone marrow derived cells that affectt he lymphatic system
what are blastomas
cancers throught to arise from immature or embryonic tissue
80-90% of acll cancers are _____
carcinomas
means that cell proliferation and frequent exposure to chemical and or physical change
how do most cancer cells originate?
- originate from a single aberrant (abnormal) cell
- abnormal cell might have been result of genetic mutation (change in cell DNA) or epigenetic mutation change in gene expression without change in DNA
*cells have normal mutation, single mutation not enought ot cause cancer its several independnt changes in cell lineage
main factors influencing tumour progression
mutation rate, number of cells in population, rate of cell division and selective advantage
what genes play a critical role in cancer developmen and progession?
- DNA proofreading and reapid genes, genes that maintain chromosomal integrity, oncogenes, tumour suppressor genes
effects of mutations in genes that regulate DNA repair
- cells susceptible to endogenous and exogenous damage throughout life cycle
- in healthy cell, damage to nuclear or mitochondrial DNA will be fixed bc rate of damage = to rate of repair
- in pathological situations rate of damage > rate of repaire
- mutations can be inherited, unstable cells are less fit and tend to aquire additional mutations in cell death, differentiation or division more frequently than normal cells
what are oncogenes
oncogenes aquire “gain of function” mutation vs tumour suppressor genes acquire “loss of function”
oncogene ex: hormones or growth factors, receptors, cell signaling molecules and transcription factors
Gain of function: mutated oncogenes are expressed at high levels resulting in cell growth and an inc in mitosis (cancer)
what are tumour suppresor genes
- kind fo like anti-oncogenes - protect cells from cancer pathology
- mutations to these genes are loss of function mutations : mutated oncogenes are expressed at high levels resulting in cell growth and an inc in mitosis
mutation in genes that normally suppress mitosis and cell growth or induce apoptosis leads to loss of function
what is the goal of cancer therapy and principles
- prevent, cure or control the disease
- for some terminal patients in palliative care it focuses on relieving and prevening suffering
Principles:
- cure requires death of ALL tumour cells
- Drugs kill a constant proportion of tumour cells
- Tumours detected later require prolonged treatment
- Drugs have narroe therapeutic index
- Drug combinations can increase effectiveness and decrease adverse effects
- Intermittent high dose therapy is more effective
- Adjuvant therapy may decrease metastases
localized vs systemic cancer treatment
- surgery and radiation = localized treatment bc its to a specific region(s) of body
- chemo and hormone therapy = systemic treatment bc they afffect all regions
*chemo can be used alone or in addition to radiation or surgery, if applied before the goal is to shrink the tumor before removing it, if applied after goal is to kill remaining cancer cells
what types of factors influencer cancer patient survival
- nature of cencer itself: typce, stage, time of diagnosis, growth rate, heterogeneity of cells within tumour and cell-cycle phase
- general health, tumour blood supply and immune status also play important roles
phases of cell division and in what phase are drugs usually most toxic?
- G0, G1, S, G2 and M phases
- many drugs are most toxic during S-phase, somewhat effective during M phase and most are ineffective during G0 phase
how does growth rate affect chemotherapy treatment?
- growth fraction refers to percent of dividing cells that ae sensitive to chemo
- addition of therapeutics during proliferative phase would allow slow growing tumours to be treated early
- early metastatic lesions have been shown to ahve a high growth fraction and fast growing cancers are more responsive to treatment
kinetics of chemotherapy
- Chemotherapy kills cancer cells via first order kinetics- eliminaition of drug is proportional to plasma conc of same drug
why do anticancer drugs fail?
due to lack of specificity (side effects and dosage limitations) or fact that cancer is resistant to treatment
- some neoplastic cells are inherently resistant others develop mutations throughout growth leading them to develop or acquire resistance
- multidrug resistance may also ocur, involved a selection of cells expressing amplified p-glycoprotein that pumps drugs out of cell
what are some of the side effects of chemotherapy?
major sites of toxicity are bone marrow (myelosuppression), Gastrointestinal tract (vomiting, nausea and diarrhea), hair follicles (alopecia), reproductive tract (dec sperm count, menopause and teratogenicity) and secondary carcinogenicity
what is most effective way of administering chemotherapy
- using in combination
- use drugs that offer synergistic action and have diff MOA and resistance pathways (no overlap in toxicities) are ideal
- want to give as close to maximal effective dose and give frequently to discourage cancer growth
what are the main factors influencing dosage of chemotherapy?
dosage is primarily based on body surface area but pharmacokinetics like hepatic and renal function also considered
- type of cancer, patient health, desire to undergo difficult/dangerous treatment and ability to cope with side effects are also important
