Cancers Flashcards
What are the lab tests for the diagnosis of cancer?
Complete blood count
Blood protein staining
Tumor marker tests
Circulating tumor cell (CTC) tests - uncommon
Explain the complete blood count test
Counts the number of different types of cells in the blood
Abnormality in number and morphology: possibility of blood cancer (leukemia, lymphoma, myeloma)
Use a bone marrow biopsy to confirm a blood cancer
Explain the RBC test
RBC count, hemoglobin (carrying prot for O2 and CO2), hematocrit (volume of blood that consist of RBC) and reticulocyte count (immature RBCs)
Use a bone marrow biopsy to confirm a blood cancer
Explain the WBC test
WBC number and differential of the groups of WBC
Monocytes, lymphocytes, neutrophils, basophils, eosinophils
- They all show up at different times during cancer
Look for abnormal numbers and shapes, and confirm with a bone marrow biopsy
What is the platelet (PLT) test?
Platelet count, mean platelet volume (avg size of platelets), and platelet distribution width (platelet uniformity)
Explain blood protein staining. How is it performed? What does it determine? Which cancers can it detect?
Serum electrophoresis
Test protein abnormality and loss of proteins
Aids in the diagnosis of lymphoma, chronic lymphocytic leukemia and multiple myeloma
What are the electrophoretic zones of blood protein staining?
Albumin (transports many molecules and drug molecules)
alpha-1 antitrypsin
alpha-2 macroglobulin
beta-1 and beta-2 transferrin (some myeloma and leuk)
gamma globulin (some myeloma and lymphoma)
What is the cancer type, sample, and purpose of the following markers: CA-125, CD25, EGFR gene mutation, Estrogen receptor.
CA-125: Ovarian cancer, blood, diagnosis and treatment
CD25 (surface protein): Non-Hodgkin lymphoma, blood, targeted therapy
EGFR gene mutation: Non-small cell lung cancer, tumor, treatment and prognosis (this one has a lower survival rate, no diagnosis purpose)
Estrogen receptor: Breast cancer, tumor, hormone therapy and targeted therapy
What is seen in CA-125 and ovarian cancer?
Cancer antigen 125 is a glycoprotein with a molecular weight greater than 200 kD
It is tested by immunoassay
Normal range in the blood is less than 46 U/mL
Cancer patients have higher than normal ranges due to ovarian cancer
What can be said about high CA-125 numbers?
The higher the number the more likelihood to be advanced stage cancer and prognosis
Ture or False: Ovarian cancer is the only reason for high CA-125 levels in the blood
False, can also be caused by other diseases that can increase levels (but not as much as cancer)
Examples include:
Endometriosis, liver disease, menstruation, pregnancy, uterine fibroids
What is the use of 70-gene signature and what stages of breast cancer are involved? What does it test?
Predicts metastasis and recurrence of breast cancer
It aids in early-stage breast cancer tx (stage 1 and 2)
It tests the activity of 70 different genes in the breast cancer tissue (<3 infected lymph nodes)
(cancer is defined by many proteins, not just one)
Explain the three liquid biopsy tests approved by the FDA
CTC test for breast, colorectal, and prostate cancer
Ferrofluid nanoparticle-based technology
What are the types of cancer diagnostic imaging?
Breast mammogram, CT scan, PET scan, MRI imaging
Explain the breast mammogram
Low dose x-ray imaging
Two images of each breast taken at approx 0.4 millisilverts
It shows abnormal areas in the breast based on images
Used for screening of breast cancer
Explain CT, PET, and MRI
Computerized Tomography (CT) = X-ray scan from different angles and computer-processed cross-sectional images
Positron Emission Tomography (PET) = use a radioactive drug as a tracer. Ex) fluorodeoxyglucose
Magnetic Resonance Imaging (MRI): uses magnetism, radio waves, and a computer to produce images (avoid wearing metal jewelry)
What is the main way to diagnose most types of cancer? Explain and provide examples
Cancer biopsy = Remove a piece of tissue from a pt’s body and analyze it in a lab
Biopsy analysis: confirmation of cancer, cancer grade (differentiated = low grade; undifferentiated = high grade), targets for targeted therapy
ex) bone marrow biopsy, endoscopic biopsy, needle biopsy, skin biopsy, surgical biopsy
What is the major therapy for cancer?
Surgery
Explain surgery for cancer tx
Remove the entire tumor (esp. early phase). It is to ease cancer sx that cause pain and pressure
Debulk a tumor = remove some but all of a tumor because entire tumor removal might damage organ. When removing a tumor we need to remove extra, healthy tissue to reduce the residual cancer cells (ex. breast tissue + surrounding fatty tissue).
Smaller residual tumor volume may be associated with longer survival for cancer patients
Breast cancer 2cm vs 20cm: smaller one has pt living two years longer
What are the types of surgery? Explain each
Open surgery -> cut open (usually done in early stages)
Minimally invasive surgery -> thru tiny incisions, non-robotic and robotic surgery
Cryosurgery -> use liquid nitrogen to tx skin cancers and retinoblastoma
Laser surgery -> on surface tumors on body, laser beam it
Hyperthermia -> radiofrequency ablation
Explain the da Vinci XI robotic surgery system
Dr uses the remote control unit, while the robotic armed unit is with the patient allowing the surgeon to be able to perform surgeries overseas
What isradiation therapy?
Apply high doses of radiation to kill cancer cells and reduce tumor size
Whats the purpose of radiation therapy?
Treatment and palliative care
What types of radiation therapy do we have available to us?
External and internal radiation therapy beam
Explain radiation therapy beam
photons - protons and electrons
3D conformal radiation therapy
Intensity-modulated radiotherapy
What is 3D conformal radiation therapy?
Allows doctors to direct radiation beams to conform the shape of the tumor.
CT scan is used to provide the 3D dimension of the tumor and nearby organs
Beams are arranged to avoid normal organs and target the tumor
What is 3D conformal radiation therapy?
Allows doctors to direct radiation beams to conform the shape of the tumor.
CT scan is used to provide the 3D dimension of the tumor and nearby organs
Beams are arranged to avoid normal organs and target the tumorWhat
What is intensity modulatedd radiotherapy?
CT scan can be used to provide the 3D dimension of the tumor and nearby organs.
Multiple beams are positioned for the therapy.
Each beam is divided into small beams
When do we use intensity modulated radiotherapy?
Used for hard to treat areas
What is brachy therapy?
a sealed container of radioactive material into the therapy
What is radioisotope therapy?
Reduce the size of the tumor such as I-131 for thyroid cancer
What is radioimmuno therapy?
Combination of radioisotopes and monoclonal antibodies
What is radioembolization?
Radioactive beads along with emobolization ( reduced blood to an organ)
True or false.
Chemotherapy is used alone or in combination with other therpais
True
What is adjuvent chemotherapy?
Often used after primary treatments sucha as surgery or radiotherapy
destroy micro-metastasis
prevent or reduce cancer reccuring
What is neoadjuvent chemotherapy?
Given before the main treatment such as surgery or radiotherapy
reduce tumor size to make primary treatment easier is more effective
What are the differnet types of chemotherapy?
- DNA-damaging agents
- Alkylating agents
- Antimetabolites
- Purine antagonists
- Pyrimidine antagonists
- Antimitotics
- Taxanes and vinca alkaloids
- Antitumor antibiotics
- Intercalating agents (anthracyclines) – doxorubicin and
daunorubicin - DNA-repair enzyme inhibitors
- PARP inhibitors 29
What functional groups do alkylating agents work on?
N7 and O6 of the guanine
What are the alkylating agents?
- Nitrogen mustards
- Melphalan, Cyclophosphamide, Ifosfamide, Chlorambucil and
Estramustine - Nitrosoureas
- Carmustine, Lomustine, Nimustine and Streptozocin (Streptozotocin)
- Platinum drugs
- Carboplatin, Cisplatin, and Oxaliplatin
- Miscellaneous alkylating drugs
- Busulfan, Procarbazine, etc.
What replaces the two clorine functional groups on the nitrogen mustard alkylating agents?
Two guanines
What functional group gets cleaved on the Streptozocin?
Methyl group attached to the nitrogen
How do the platinum alkylating agents work?
Alkylate and crosslink DNA (intra and inter)
cell cycle non specific
True or false
DNA-protein cross links are very common with platinum alkylating agents
False
They are not common
Explain busulfan MOA?
remove mesylate(CH3 SO3-) to form R-CH2+ ( non specific alkylating agent
What conditions do we use busulfan to treat?
Chronic myelgenous leukemia
Explain procarbozine MOA?
The methyldiazonium ion (CH 3-N+≡N) and methyl cation (CH 3+) gets dealkylated
Non specific alkylating agent which methylates guanine at O6
What type of synthesis does procarbozine inhibit?
Protein - RNA - DNA
In what conditions do we use procarbozine?
Hodgkin’s lymphoma (stages III and IV), non-hodgkins lymphoma and gliomas
What are antimetabolites?
prevent the biosynthesis of normal cellular metabolites
What are some types of antimetabolites?
Pyrimidine a. - purine a. - fulic acid analouges …
What is the main antimetabolite?
Uracil
What is the MOA of antimetabolite Cytrabine?
Inhibit the conversion of cytidylic acid to 2’-deoxycytidylic acid
DNA dependent DNA polymerase
Miscoding due to incorporation into DNA/RNA
Effective during S-Phase -> cell apoptosis
Name two types of antimitotics and their site of action?
Paclitaxel = breast, lung, and ovarian cancers
Docetaxel = breast, lung, stomach, prostate, and head and neck
cancers
What is the mechanism of action of antimitotics?
bind to free tubulin
produce stable microtubules
inhibit microtuble disassembly (major function)
microtubules arrange in a parallel fashiom rather than a spindle
What are some vinca alkaloids?
Vinblastine, vincristine, vindesine and vinorelbine
What do vinca alkaloids prevent?
Microtube polymerization
True or false.
Vinca alkolides have the opposite MOA of taxanes
True
what conditions do vinca alkaloids treat?
Hodgkin’s lymphoma, non-small cell lung
cancer, bladder cancer and melanoma
What is the dosage form of vinca alkolides?
IV
What are some antitumor antibiotics?
Daunorubicin, doxorubicin, epirubicin, idarubicin and
mitoxantrone
What do anthracyclines do ?
DNA intercalating agents
What’s the MOA of anthracyclines?
- Intercalate with DNA perpendicular to its longitudinal axis
- Cause single and double stranded DNA cleavage
What are PARP and PARP inhibitors? Provide the drug MOA
PARP = Poly(ADP-ribose) polymerase
-> its main fxn is involved in DNA repair
PARP inhibitors are DNA repairing enzyme inhibitors
-> they block DNA repair in cancer cells and cause cancer cell death (PARP is overexpressed in many cancers)
What happens to our normal cells in the body during PARP treatment?
Nothing, the drug only targets PARP which is only in cancer cells
Our cells have different repair systems
What is targeted therapy and what are the goals of targeted therapy?
To slow down cancer growth, kill cancer cells, and relieve sx caused by cancer
We can use small molecule agents and monoclonal antibodies to do this
What are the four main examples of targeted therapy agents?
Tyrosine kinase inhibitors (TKIs) -tinib
Monoclonal antibodies -mab
Apoptosis-inducing agents (bortezomib and oblimersen)
Angiogenesis inhibitors (bevacizumab and sunitinib)
What is the TK domain?
The tyrosine kinase domain is present in growth factor receptors, such as epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR), and signaling protein kinases such as Ras and Raf
What does imatinib treat? How does it work?
Treats chronic myelogenous leukemia (CML) and acute lymphocytic leukemia (ALL)
It inhibits BCR-ABL tyrosine kinase and inhibits proliferation and induces apoptosis in BCR-ABL positive cells
What is gefitinib prescribed for? How does it work?
It is for non-small cell lung cancer (NSCLC) with EGFR exon 19 deletion or exon 21 L858R mutation
It inhibits epidermal growth factor receptor (EGFR). Blocks it
What does EGF-EGFR signaling promote?
DNA synthesis, proliferation, migration, and survival of cells
From the image: proliferation, invasion, angiogenesis, metastasis, resistance to apoptosis
What does the monoclonal antibody trastuzumab target? Explain the significance of the target
Her2
Her2 is highly expressed in breast cancer patients
Where does trastuzumab bind to?
Binds to the subdomain IV of Her2 protein (the protein helps with the dimerization of Her2)
What type of drug is pertuzumab and where does it bind to? What is the function of the drug?
It is another monoclonal antibody
Binds to the subdomain II of Her2 protein
Blocks homodimerization of Her2 and heterodimerization of Her2-Her3
Inhibits Her2-singalling pathway and decreases cells growth
What can be used for metastatic and recurrent Her2+ breast cancer?
Trastuzumab + pertuzumab + docetaxel
What is T-DM1?
Ado-trastuzumab emtansine, it is a conjugate of trastuzumab and emtansine
it treats Her2+ metastatic breast cancer and early-stage Her2+ breast cancer after surgery
What is Emtansine of T-DM1?
It is a potent cytotoxic agent, it cleaved from T-DM1 and release inside breast cancer cells
What are apoptosis-inducing agents? Provide an example
Proteasome inhibitor and apoptosis-inducing agent
Binds to 26S proteasome, prevent proteosome-mediated degradation of pro-apoptotic factors and induce apoptosis (we are keeping/saving the proteins that induce apoptosis)
Ex) Bortezomib
What can apoptosis-inducing agents treat?
Treat multiple myeloma and mantle cell lymphoma (B-cell non-Hodgkin lymphoma)
the difference bet Hodgkin and non-Hodgkin is the presence of Reed-Sternberg cells (lymphocytes with 2-3 nuclei inside)
What do angiogenesis inhibitors do? Provide an example
Block vascular endothelial growth factor (VEGF)
VEGF and its receptors can induce and promote angiogenesis
The ultimate goal here is to starve cancer cells
Ex) bevacizumab
What can angiogenesis inhibitors treat?
Various types of cancer such as colon cancer and lung cancer
What is sunitinib?
Multiple-targeted tyrosine kinase inhibitor
Inhibits VEGFR (receptor), platelet-derived growth factor receptor (PDGFR), colony stimulating factor receptor (CSFR) and tyrosine-protein kinase KIT (CD11&)
Angiogenesis inhibitor
What can sunitinib be used to treat?
Prescribed for renal cell carcinoma, imatinib-resistant gastrointestinal stromal tumor and metastatic pancreatic cancer
What is immunotherapy?
Stimulate immune system to fight cancer
What are the immune system components?
Surfaces - protect body against foreign substances
- Skin, mucous memb, tonsils
Internal organs
- Spleen, thymus, bone marrow, lymph nodes
Compare and contrast the innate immune response and the adaptive immune response
Innate:
nonspecific immune response
response is immediate
recruit immune cells to infxn site to release chemical factors such as cytokines
send antigens to adaptive immune sys
Adaptive:
create immunological memory
recognize specific antigen
takes 4-7 days to respond
What are the cells that overlap between the innate and adaptive responses?
T cell and Natural killer T cell
What is PD-1?
PD-1 = programmed cell death protein 1
Surface protein on T-cells
Prevents T-cells from other cells upon binding PD-L1
Check immune responses
What are PD-L1 cells?
Programmed cell death ligand 1
Prevents T-cells from killing PD-L1 containing cells (ex. pregnant woman - we don’t want immune sys to attack the baby)
upregulated in cancer cells
Explain hormonal therapies
Hormones can bind estrogen receptor (ER) and progesterone receptor (PR) to promote cancer cell growth
Hormonal therapies are used for breast cancer cells with the expression of ER and PR
What is Tamoxifen?
It is a hormonal therapy
Blocks ER and inhibits breast cancer cell growth
May slightly increase the chance of getting uterine cancer
Name the three PD-1 inhibitors
Pembrolizumab
Nivolumab
Cemiplimab
Name the three PD-L1 inhibitors
Atezolizumab
Avelumab
Durvalumab
