Lec 5 - Cancer treatment and classiciation

What are some ways we can suppress cancer besides chemotherapy? (4)

1. tyrosine kinase inhibitors

2. histone deacetylase inhibitors (SIRT pathways)

3. angiogenesis inhibitors

4. immunotherapy

Reduce cell proliferation and increase apoptosis

What is tyrosine kinase? What will tyrosine kinase inhibitors do?

Tyrosine Kinase promotes survival and proliferation of some cells

TK is over-active in cancer cells

• May play a role in modulating p53 as well

TK inhibitors will decrease this activity

• Block signal pathways that cause cells to proliferate - stop pathway for cell division

• upregulate pathways that cause apoptosis

What do Histone deacetylase inhibitors do? How does it work?

Plays important role in gene expression

• Abnormal activity of HATs (histone acetyltransferase) or HDACs (histone deacetylase) can either promote or inhibit suppessor or promotor genes

• Factor in acute promyelocytic leukemia, acute myelogenous leukemia, non-Hodgkin lymphoma, and some types of colorectal and gastric carcinoma

May re-sensitize cells to drugs, chemotherapy

• Can affect expression of suppressor genes (epigenetic)

What is angiogenesis? What do angiogenesis inhibitors do? **exam

This is a vital in tumour growth

• provides oxygen and nutrient supply

• allows for metastasis

Inhibitors reduce formation of blood vessels (choking cells, by cutting off blood supply)

• Limit growth and metastasis

• Eg. Vasostatin, Angiostatin, Thalidomide, Sorafenib

What is immunotherapy?

AKA biologic therapy which boost body’s own immune response

• Recognition of cancer cells

• Slow or stop growth of cells/ kill cells

Stimulating immune response to cancer cells

What are some immunotherapy treatments? **exam (know each and one sentence describing what each is )

1. monoclonal antibodies

2. oncolytic virus therapy

3. t-cell therapy

4. cancer vaccines

What is interferon/interleukins therapy treatment? What does each do and how?

Are cytokines in the immune response

Interferons increase resistance in normal body cells

• Blocks growth of cancer cells

• Causes cancer cells to send out cytokines (identifiers)

  • Makes cancer cells more susceptible to the cytotoxic (killer) T cells

Interleukin 2 increases activity of T-cells

• Inhibits growth in cancer cells

Can be used in most cancers

What are monoclonal antibodies?

Lab-made antibodies

• Can increase body’s own antibodies and response

• Can block protein activity in cancers (targeted therapy)

Cancer cells “hide” by activating immune checkpoints

• Body uses these normally to recognize its own cells

Antibodies can turn off these checkpoints

• Amplify bodies response to the cancer

• Eg.Ipilimumab, Nivolumab Avelumab Durvalumab

How are monoclonal antibodies made? What do they help to do?

Made from clones of one cell (antigen)

Help to bind Killer T cells

Help to bind radioactive and immunotoxins

Can trigger apoptosis

What is targeted therapy? Exmaple?

Therapies are specific to the genetic changes in that tumour, rather than just location in body

• Can target proteins specific to the cancer

• Eg. Monoclonal antibodies can attack

Small synthetic molecules

• Block or turn off cell growth and division signals

• Shorten cell lifespan

• Directly destroy cancer cells

What is oncolytic virus therapy? What cancer was it used for?

Inject a genetically modified virus into tumour

• doesn’t enter healthy cells

Virus enters the cancer cells to replicate

Causes cancer cells to rupture and die

• proteins released from dying cells trigger immune system to target any cancer cells that have the same proteins

May cause symptoms – fever, fatigue, nausea

Has been used on melanomas

• Clinical trials for others

What are challenges with oncolytic virus therapy? (2)

Innate immune response may attack the virus before entry or before immune response is developed

Tumour may suppress immune response

What is t-cell therapy? What cancer is it used for?

Aka chimeric antigen receptor (CAR) T-cell therapy

Remove patients’ T-cells (cancer cells or WBC…)

• Modify / add receptors that will recognize the cancer cells

• Re-inject into patient to kill cancer cells

• May trigger fever, seizure, confusion,

Can be used for blood cancers

• Testing being done on other cancers

What are types of cancer vaccines? (2)

Treatment vaccines

• Expose body to cancer cells or proteins (antigens) or DNA segments to trigger an immune response

• Being studied

Preventive

• Eg. HPV vaccine

  • Prevents viral infection that can be causative in cancer

What are the top age-related cancers? (5)

1. lung

2. breast

3. prostate

4. colorectal

5. bladder

What is the fastest increasing cancer in Canada?

Melanomas

• more so on east than west

• can be higher in AB due to out altitude

What cancers have the poorest survival rate?

Pancreas and lung cancers

• breast cancer rates have decreased by a lot

What are the general risk factors for cancers? (7)

1. Genetics

2. Aging

3. Diet / Exercise / obesity

4. Alcohol

5. Smoking

6. Ethnicity

7. Chronic inflammation

   1. Pre-existing diseases

What is hyperplasia in cancer?

Overgrowth of cells

• Triggered by stimulus

• (eg. Hormones, pressure, deficiency)

Stops when stimulus removed

What is neoplasm in cancer?

Independent and excessive growth

Cells are different in appearance

• abnormal cells

What is neoplasia?

Tumour

• Fast growth of cells

• grow more rapidly than normal cells

What are characteristics of benign tumours? **exam

1. tumour is encapsulated and has clearly defiend edges

2. doesn’t metastasize and has limited growth potential (grows slower)

3. differentiated - resembles tissue from which it grew

   1. like dysplasia and hyperplasia…

What are characteristics of malignant tumours? **exam

1. invades normal tissue - no encapsulation

2. does metastasize and forms tumours in distant locations (cells pull off)

3. abnormal tissue - rapid, uncontrolled growth

   1. neoplasia…

How can neoplasms be classified? How are they classified? **exam

into benign or malignant (cancer)

Malignant has 3 types

• epithelial (carcinomas)

• connective tissue (sarcoma)

• leukemias (blood cancer)

Classified according to:

• Appearance and growth pattern

• Type of body tissue from which they arise

What is carcinoma? **exam

• neoplasm of the epithelial cells

• Largest group of malignancy

• Skin as well as epithelial linings (mucous membranes etc.)

What is adenocarcinoma?

Occurs in epithelial tissues with glandular origin

• type of carcinoma

What is sarcoma? Mixed cancer? **exam

Sarcoma

• Neoplasms of connective tissue

Mixed Cancer

• epithelial and connective tissue

What are tumours? (3) **exam

Melanoma

• Malignant neoplasm of melanocytes

Glioma

• tumours of glial cells of brain

Lymphoma

• neoplasms of Lymphoid tissue and blood-forming organs

What is leukemia? **Exam

Happens in white blood cells

• can be lymphocytic leukemia or myelocytic leukemia

When does cancer present as we age?

Peak age of diagnosis – age 65

Cancer cell growth can slow down after the age of 75

• Lower metabolic rates with age

How can cancer invade and metastasize? (3 examples)

Carcinomas and epithelial tissue neoplasms commonly spread

Sarcomas shed cells into bloodstream

Lymph nodes filter cancer cells

• Absence of lymph node involvement favourable