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Flashcards in Final Exam (Pt. 3) Deck (24):
1

Cancer

Group of disease involving abnormal cell growth with potential to invade or spread to other parts of the body. 

2

What are the two types of cancerous tumors?

  • Malignant Tumor: potential to invade or spread (metastasize).
  • Benign Tumor: self-limiting and grows slowly. 

3

What are the factors that can lead to cancer?

Both genetic and environmental (e.g. smoking, UV radiation). Although "somatic" in origin, it does have a heritable genetic component.

4

Why is cancer a multi-hit phenomenon?

Multi-hit phenomenon (many genes need to be mutated), and there are a wide variety of genes that have been associated with cancer; transcription factors, epigenetic factors, signaling factors, DNA damage repair factors, regulators of cell death.

5

What are main types of genes that are generally assocaited with cancer?

Both proto-oncogenes (e.g. c-Myc, c-Myb [transcription factors) as well as tumor suppressors (e.g. RB, p53 [transcription factors]; BRCA1 and 2 [DNA damage repair factors]

6

What seperates proto-oncogenes and tumor suppressors?

The former when mutated promote cancer (oncogenes: e.g., RAS Family [signaling factor gene; GTPases], HER2, RET, PTC [signaling factors gene: receptors], SHH [signaling factor: ligand], c-Myc, c-Myb [transcription factors]) while the latter puts the brakes on cell division.

7

What are some epigenetic factors involved in cancer?

Epigenetic factors include CBP and P300 (histone actyl transferases), EZH2 (methyl transferase), fusion of HDACs to transcription factors.

8

What are protein kinases and cell death regulators that involved in cancer?

Protein kinases include FGFR2, ATM, BRAF, ABL, SRC; regulators of cell death include BcL-2. 

9

How does targeted therapy work against cancer

Most targeted therapies help treat cancer by interfering with specific proteins that help tumors grow and spread throughout the body. They treat cancer in many different ways:

  • Help immune system destroy cancer cells
  • Stop cancer cells from growing
  • Stop signals that help form blood vessels
  • Deliver cell-killing substances to cancer cells.

10

How does the targeted therapy help the immune system destroy cancer cells?

One reason that cancer cells thrive is because they are able to hide from your immune system.

Certain targeted therapies can mark cancer cells so it is easier for the immune system to find and destroy them.

Other targeted therapies help boost your immune system to work better against cancer. Example:

Monoclonal antibodies against specific molecules on cancer cells; also, CAR T, which is immune system technology v2!

11

How does targeted therapy help stop cancer cells from growing?

Healthy cells in your body usually divide to make new cells only when they receive strong signals to do so.

These signals bind to proteins on the cell surface, telling the cells to divide.

But, some cancer cells have changes in the proteins on their surface that tell them to divide whether or not signals are present.

Some targeted therapies interfere with these proteins, preventing them from telling the cells to divide.

This process helps slow cancer’s uncontrolled growth.

Example: Signal transduction inhibitors, including monoclonal antibodies or drugs (gefitinib) that are competitive inhibitors of ATP binding sites on tyrosine and serine/threonine kinases (thus, phosphate groups can’t be added to targets).

12

How does targeted therapy stop signals that help form blood vessels?

Tumors need to form new blood vessels to grow beyond a certain size.

These new blood vessels form in response to signals from the tumor.

Some targeted therapies are designed to interfere with these signals to prevent a blood supply from forming.

Without a blood supply, tumors stay small. Or, if a tumor already has a blood supply, these treatments can cause blood vessels to die, which causes the tumor to shrink.

Example: Interfering with vascular endothelial growth factor (VEGF). One example of this is the drug bevacizumab, which binds to VEGF and inhibits its binding to VEGF receptors.

13

How does targeted therapy deliver cell-killing substances to cancer cells?

Some monoclonal antibodies are combined with toxins, chemotherapy drugs, and radiation.

Once these monoclonal antibodies attach to targets on the surface of cancer cells, the cells take up the cell-killing substances, causing them to die.

Cells that don’t have the target will not be harmed.

Example: Antibody-drug conjugates, which are currently in the clinic; Brentuximab vedotin delivers the potent and highly toxic antimicrotubule agent monomethyl auristatin E (MMAE) to CD30-positive malignant cells.

14

What are some drawbacks of targeted therapy?

Cancer cells can become resistant to them. For this reason, targeted therapies may work best when used with other targeted therapies or with other cancer treatments, such as chemotherapy and radiation.

Drugs for some targets are hard to develop. Reasons include the target’s structure, the target’s function in the cell, or both.

15

Monoclonal Antibodies (Immunotherapy)

Monoclonal antibodies, which are drugs that can “mark” cancer cells so it is easier for the immune system to find and destroy them. These types of monoclonal antibodies may also be referred to as targeted therapy.

16

Adoptive Cell Transfer (Immunotherapy)

Adoptive cell transfer, which is a treatment that attempts to boost the natural ability of your T cells to fight cancer.

Researchers take T cells from the tumor, then isolate the T cells that are most active against your cancer or modify the genes in them to make them better able to find and destroy your cancer cells.

The T cells are then grown in large batches in the lab and given back to you intravenously.

17

Cytokines (Immunotherapy)

Cytokines, which are proteins that are made by your body’s cells.

They play important roles in the body’s normal immune responses and also in the immune system’s ability to respond to cancer.

The two main types of cytokines used to treat cancer are called interferons and interleukins.

18

Treatment Vaccines (Immunotherapy)

Treatment Vaccines, which work against cancer by boosting your immune system’s response to cancer cells.

Treatment vaccines are different from the ones that help prevent disease.

19

BCG (Immunotherapy)

BCG, which stands for Bacillus Calmette-Guérin, is an immunotherapy that is used to treat bladder cancer.

It is a weakened form of the bacteria that causes tuberculosis.

When inserted directly into the bladder with a catheter, BCG causes an immune response against cancer cells. It is also being studied in other types of cancer.

20

CAR T-cell Therapy

Form of adoptive cell transfer also called a living drug; a type of treatment in which a patient's T cells are altered in the laboratory so they will attack cancer cells. In the first step, T cells are taken from a patient’s blood.

21

How is the T-cell modified in the lab?

The gene for a special receptor that binds to a certain antigen on the patient’s cancer cells is then inserted into the cellular DNA using retroviral vectors.

The special receptor is called a chimeric antigen receptor (CAR) which is an artificial T cell receptor and combines antigen-binding and cytotoxic T-cell activating function

22

How are the T-cells administered?

Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion.

23

For CAR T-cell therapy, what is the protein only found on cancer cells?

For B cell malignancies (acute lymphoblastic leukemia, chronic lymphoblastic leukemia, forms of Hodgkin’s lymphoma), CD19 is the target since B cells specifically express CD19 (adapter protein to recruit signaling proteins).

24

What are the side effects of CAR T?

Side effects include high fever, fatigue, cardiac dysfunction, hepatic failure, renal impairment, cytokine release syndrome, etc.