Anti-Cancer Drugs - Part 1

A general term used to denote any of the many different forms of tumors, or an abnormal growth of cells is…

Cancer

In the early 1900s: two main theories on oncogenesis emerged. What were they?

1. External agents cause cancer

2. Cancer is a result of inborn errors

What are some general characteristics of a cancer cell? (stability of genes, life span, contact inhibition, growth factors?)

1. Genome instability

2. Infinite life span

3. Loss of normal growth constraints (decreased growth factor dependence, loss of contact inhibition, anchorage independent growth)

4. Morphological changes

What are the two structures of human organs that cancer can occur in? Which do most cancers grow in?

1. Epithelium and Mesenchyme

2. Epithelium - most cancers occur in

Cancer is primarily a disease state of the ______

Elderly

What is the most common cancer in all ages? What is most popular in children under 15? What is most common for females 15-54?

1. Lung cancer

2. Leukemia

3. Breast cancer

Describe the age-specific incidence of cancer of the colon as people age?

How many deaths of cancer per year?

Incidence rates increase

10,000,000 deaths per year

Cancer by the numbers: describe cure rates over time (1953 to 2015)

1. 30% cure rate = 1953

2. Cancer mortality declines = 1991

3. Absolute deaths decline = 1997

4. 60% cure rate = 2002

5. Cancer death rate declines 26% = 1991 to 2015

The transformation of normal to neoplastic cells is caused by what types of agents (general groups (2) and specific agents)?

1. Endogenous and exogenous

2. Chemical/physic agents

3. Viruses, bacteria, parasites

What type of models created in the 1970s were the first reproducible models of carcinogenesis, which identified carcinogens and the metabolic steps/targets to activate them.

Animal models of carcinogenesis

The initial multistage models of carcinogenesis can be divided into what 3 stages?

1. Initiation

2. Promotion

3. Progression

A ______ can be converted into an active oncogene by a ________ mutation, which results in altered or increased gene product activity

1. Proto-oncogene → oncogene

2. By a genetic mutation

Name 3 examples of genetic mutation that can convert a proto-oncogene into an oncogene?

1. Gene Amplification

2. Chromosomal translocation

3. Gene mutation (base substitution)

What is a tumor suppressor gene?

1. Gene whose product is NECESSARY for normal cell function

   1. Loss of function causes or contributes to tumor phenotype

   2. Both copies of TSG must be inactivated to reveal tumor properties

What are some common mechanisms of tumor suppressor gene inactivation? Name 4 tumor suppressors?

1. Gene deletion - physical loss of gene

2. Gene mutation - produces protein product (not functional)

3. Epigenetic inactivation - aberrant, reversible chemical modifications - result in tumor suppressor gene silencing

Tumor suppressors: Rb, p53, BRCA1, p16

Cancer is a disease of DNA. There is strong evidence that specific _______ can induce mutations in somatic tissue that drive specific cancers

Genotoxins can induce mutations

Cancer can be classified into two heritable properties:

1. Proliferative capacity that ______________

2. Ability to invade ___________

1. Proliferative capacity that no longer responds to normal growth controls

2. Ability to invade and colonize surrounding tissue, as well as distant sites

What are benign tumors?

1. May arise in ANY TISSUE

2. Grows locally - does not invade other tissue

3. Can be surgically removed with no recurrence

What is carcinoma in situ?

1. Epithelial in origin

2. Morphologically similar to cancer

3. Non-invasive (premalignant lesion)

What are malignant tumors?

1. Generally more serious than benign tumors

2. Potentially life threatening

3. Can be surgically removed, able to invade surrounding tissue/blood

4. Can damage local and distant tissues/organs

5. Forms secondary tumors (metastases)

Describe cancer nomenclature…

1. -oma = tumor

2. Epithelial benign tumors = papilloma, adenoma

3. Malignant epithelial tumors = Carcinoma

4. Mesenchymal benign cancers = osteoma, fibroma

5. Malignant mesenchymal tumors = Sarcoma

Hematopoietic system: Cell lineage of origin, divided into what two categories?

1. Leukemias = myeloid

2. Lymphomas = lymphoid

Tumors of neurons (nervous system) occur when?

These include neuroblastoma or retinoblastoma

Appear only shortly after birth

Among the most common form of brain tumors seen in adulthood, all other arise from supporting ______ cells. Name an example.

1. Glial cells

2. Astrocytes

What is the TNM system?

1. Assessment of primary Tumor

2. Assessment of regional lymph Nodes

3. Presence or absence of Metastases

What are the 3 tumor grades?

Grade 1: well differentiated

Grade 2: medium differentiation

Grade 3: poorly differentiated

What Patient Staging tool is a standard way of measuring the ability of cancer patients to perform ordinary tasks?

1. Karnofsky Performance Status

2. Range from 0-100

3. Higher score - can better carry out daily activities