Oncology Midterm #2 Flashcards
Oncology Agents
Selectivity is incredibly important but the ability to only kill cancer cells is impossible.
Cytotoxic agents: kill cancer cells, first agents developed. Cause necrosis
Cytostatic agents: inhibit the growth of cancer cells. Less toxic. Cause apoptosis
Carcinogenesis
- Under normal circumstances cells in the human body are under strict control in terms of growth and differentiation, which are stimulated by growth factors.
- apoptosis: organized and programmed cell death. Normal cell maintenance in healthy tissue
- Hallmark of cancer is uncontrolled growth of abnormal cells which consume nutrients and energy within the host, and the cancer cells lose their ability to perform their normal functions1
Solid vs Liquid
solid tumors: cancer cells are located in solid tissues, not as responsive to radiation
liquid tumors: cells in the blood, responsive to radiation
Oncogenes vs Tumor suppressor genes
Oncogenes: mutation that occurs in proto-oncogenes, which promote cancer. Regulate the communication between cells and their outside environment
Tumor suppressor genes: mutations occur in these genes these genes normally suppress cancer, and when mutated they lack the ability to “turn off” cancer
Types of mutations
inherited germ line mutations, spontaneous point mutations, chromosomal rearrangements or augmentation of gene expression
Chronic myelogenous leukemia (CML) mutation
bcr-abl translocation (oncogene), Philadelphia chromosome. Liquid tumor. gene rearrangement, part of chromosome 22 is translocated to chromosome 9 to turn on cell growth. Chromosome 9 gets longer and chromosome 22 gets shorter.
Cell Cycle stages
somatic cell division through mitosis
G0: resting phase
G1: initial phase of mitosis; synthesis of enzymes required for DNA synthesis (about 20 hours)
S: DNA synthesis and replication of DNA (about 20 hours)
G2: synthesis of RNA, protein and formation of mitotic spindle for duplication of the cell (2-10 hours)
M: mitosis (1 hour) forming 2 daughter cells that are clones of the mother cell.
Polytherapy
Combining drugs that work at different phases of the cell cycle for greater cell kill
Cell cycle specific drugs: anti-cancer drugs that are specific for a certain phase in the cell cylce.
Antimetabolites: damage cells in the S phase
Antimitotics: Damage cells in the M phase
Metastasis
process by which cancer cells leave the location of the parent tumor and spread to distant sites.
Bloodstream and lymphatic system are the primary distributors.
Primary tumor must slough off enough cells to allow one to travel to another site.
Liver is common, highly perfused. Same with lung, brain and bone marrow.
Most cancer patients die from the consequences of metastatic lesions rather than the parent tumor.
Circulating tumor cells (CTCs)
type of cell that is sloughed from the primary cancer tumor. Measurement is used as a prognostic factor and a diagnostic factor and they are considered biomarkers or surrogate markers.
Chemotherapy as treatment
One of the four major forms: surgery, radiotherapy, biological (bone marrow transplantation or stem cell transplantation) and chemotherapy
Cancer cells are not “intelligent” but they are “adaptive”. They survive by clonal selection and they use many mechanisms to survive. This is why we use polytherapy in treatment of cancer. Single agent therapy may be successful in early stage hormone dependent cancers like breast and prostate.
Premedications
Minimize the occurrence of side effects and hypersensitivity
H1 antagonist: diphenhydramine
H2 antagonist: ranitidine
Corticosteroids: dexamethasone
Antiemetics for N/V
Drug Resistance
Occurs because not all cancer cells in a given tumor are exactly alike.
Clonal selection: the cells most sensitive to the initial drug dies but the resistant cells survive and continue to grow and replicate
Prostate cancer example: Androgen dependent cells and androgen independent cells. With hormone withdrawal kill all of the AD cells but leave the AI cells. Tumor returns containing mainly AI cells.
Clinical trials:
Phase 1 focus on PK and dose-limiting toxicities (10-25 subjects).
Phase 2 focus on signs of efficacy (30 patients).
Phase 3 focuses on proof of efficacy and frequency of side effects (100’s or 1000’s subjects).
Response criteria in early phase trials (Phase 1 and 2):
Complete response (CR): no sign of cancer 1 month after completion of therapy
Partial response (PR): reduced tumor size of 30% or more
Stable disease (SD): tumor size has not increased more than 20% and decreased less than 30%
Progression (P): tumor has grown by more than 20% and/or formation of new lesions
Response criteria for final stage trials (phase 3)
Overall survival (OS): how much longer do patients survive on average. gold standard.
Progression free survival (PFS): how much longer patients survive without progression (worsening) of disease.
Personnel:
surgical oncologists, radiation oncologists, hematologic oncologists (largely liquid tumor), medical oncologists (largely solid tumor), oncology pharmacists, oncology nurses, oncology histopathologists and geneticists. Oncology pharmacists should pay attention to drug interactions and combined toxicities.
Incidence
Use American Cancer Society for incidence and mortality
Most common: breast cancer, colorectal cancer, lung cancer and prostate cancer
Most lethal cancers: esophageal, glioblastoma (type of brain cancer), liver and bile duct and pancreatic. Also very rare cancers have high mortality because it is hard to conduct clinical trials for new treatment.
Hematopoeisis
the process by the blood cell components are produced in the body.
Different cell types are produced down different paths and can be stimulated or inhibited differently
Amount of cell types in body
Humans normally have approximately 5 million RBCs, 150,000-400,000 platelets and 4,000-11,000 WBC (which are subdivided into different populations). Low numbers of WBC make them vulnerable to depletion and they are necessary to prevent infection.
Formation of hematopoetic cells
Hemocytoblast forms all the different blood cell types. Leukocytes are white and include granulocytes and agranulocytes. Erythrocytes are red. Thrombocytes are platelets.
RBCs (erythrocytes)
Primary function is oxygen transport, Very rich in the oxygen carrier hemoglobin
Production can be stimulated by low oxygen content in blood which is detected in the kidneys. The kidney stimulates secretion of erythropoietin (Epo) which increases RBC production
Life-span is 120 days
WBC (leukocytes)
Primary function is to fight infection, and there are many subtypes
life-span is hours to several days or a weeks
Granulocytes and Agranulocytes
Granulocytes:
have the appearance of granules in their cytoplasm.
Granules are packets of digestive enzymes. Three subtypes:
- Neutrophils: target bacteria and fungi and destroy these pathogens by phagocytosis
- Eosinophils: target parasites and involved in allergic inflammatory responses
- basophils: store histamine for release during inflammation response. Hives, anaphylaxis











































