Heemer- oncology overview/intro- EXAM 1

What is cancer?

• uncontrolled cell growth

• local tissue invasion

• distant metastases

What are the 4 most common cancers? Which causes the most deaths?

• prostate

• breast

• lung- most deaths

• colorectal

Is carcinogenesis fully understood?

no

What are the 4 steps of carcinogenesis? Explain each.

1. initiation- exposure of normal cells to carcinogens—> genetic damage results if not repaired

2. promotion- carcinogens alter environment to favor growth of mutated cells > normal cells

3. conversion/transformation- when mutated cells become cancerous

4. progression- further genetic changes leading to increased cell proliferation—> 2 critical elements: invasion into local tissues and development of metastases

What step of carcinogenesis is A REVERSIBLE PROCESS?

promotion step

Carcinogens can be chemical, physical, or biologic. What are examples of PHYSICAL carcinogens?

ionization radiation and ultraviolet light

Carcinogens can be chemical, physical, or biologic. What are examples of BIOLOGIC carcinogens?

viruses

How does ionizing radiation and ultraviolet light cause cancer?

induce mutations by forming FREE RADICALS

What are factors that promote carcinogenesis?

• age

• gender

• diet

• growth factors

• chronic irritation

What project helped us understand genetic changes that lead to cancer?

Human Genome Project

What are the 2 major classes of genes involved in carcinogenesis?

1. oncogenes

2. tumor suppressor genes

Answer the following about Oncogenes:

• Oncogenes develop from normal genes called __________.

• Once activated, oncogenes produce what?

• What is the result of oncogenes being activated?

• What is an example of an oncogene?

• Oncogenes develop from proto-oncogenes

• once activated, oncogenes produce excessive amounts of a normal gene product OR abnormal gene product

• the result of oncogenes being activated: dysregulation of normal cell growth/proliferation

• ex: “HER” family

Answer the following about tumor suppressor genes:

• function?

• result of gene loss/mutation?

• example?

• function: regulate and inhibit inappropriate cell growth/proliferation

• result of gene loss/mutation: loss of control over normal cell growth

• example: retinoblastoma and p53 genes

Together, tumor suppressor genes and oncogenes provide stimulatory/inhibitory signals that regulate the _______________.

cell cycle

Is a single gene mutation enough to initiate cancer?

NO!!!! must be a combination of mutations

Identifying genes like tumor suppressor genes and oncogenes are important in…

cancer screening and designing new anticancer drugs

Tumors originate from what tissues?

basically ANY TISSUE!!! (epithelial, connective, lymph, nerve)

In some cancers, we see cellular changes before the cancer is actually malignant (deadly). These cellular changes can either be ________ or __________ . Describe each.

HYPERPLASIA OR DYSPLASIA

• hyperplasia- increase in the # of cells in a tissue/organ, results in increased size of organ

• dysplasia- abnormal changes in size, shape, or organization of cells/tissues

What are malignant growths that arise in EPITHELIAL CELLS?

carcinomas

What are malignant growths that arise in muscle/connective tissue?

sarcomas

What is “carcinoma in situ”?

cancer is limited to epithelial cells of origin (not yet invaded the basement membrane), preinvasive stage of malignancy. (also known as T_is)

A TUMOR CAN EITHER BE _____________(noncancerous) or ______________ (cancerous). Describe each.

BENIGN OR MALIGNANT!!!!

• benign- noncancerous, localized, rarely metastasize

• malignant- invade and DESTORY surrounding tissue, GENETICALLY UNSTABLE, anaplasia, METASTASIZE

What is metastasis and what are the 2 primary pathways?

metastasis is the spread of neoplastic cells from primary tumor to distant sites.

2 pathways are hematogenous or lymphatic.

Explain the 3 STEP PROCESS of metastasis:

1. angiogenesis

   • after neoplastic transformation—> malignant cells and host tissue stimulate formation of new blood vessels for oxygen & nutrients known as angiogenesis/neovascularization

2. invasion and fight

   • Tumor cells detach from main mass and invade surrounding tissues, must fight host immune system

3. repeat step 1

   • as the cancer spreads must go through angiogenesis in each new spot

For cancer in adults, what are the general symptoms? (i don’t know how imp)

Adult – “CAUTION”

• Change in bowel/bladder habits

• A sore that doesn’t heal

• Unusual bleeding/discharge

• Thickening/lump in breast or elsewhere

• Indigestion or dysphagia

• Obvious change in wart/mole

• Nagging cough/hoarseness

For cancer in kids, what are the general symptoms? (i don’t know how imp)

Children—“CHILDREN”

• Continued/unexplained weight loss

• Headache w/ vomiting in the morning

• Increased swelling/persistent pain in bone/joints

• Lump/mass

• Development of whitish appearance in eye pupil

• Recurrent fevers not caused by infections

• Excessive bruising/bleeding

• Noticeable paleness/prolonged tiredness

What is the role of tumor markers? Are they specific or nonspecific?

• role- HELP DIAGNOSE and to monitor tx

• NONSPECIFIC

What is TNM?

most common staging system for SOLID tumors

Explain each component of the TNM staging system:

T= tumor (size)

N= nodes (# of nodes)

M = metastases (present or not)

What is a sentinal lymph node?

the first lymph node to which cancer cells are most likely to spread from a primary tumor

Most cancers are stages I-IV. Briefly describe each stage:

Stage I- localized tumor

Stage II- local extension of disease

Stage III- regional extension of disease

Stage IV- indicates presence of distant metastases

What are the primary methods of cancer treatment? Which is the tx of choice for solid tumors in early stages?

• surgery—> usually tx of choice for early solid

• radiation—→ used a lot in the management

• anticancer therapy

  • chemo

  • targeted agents

  • immunotherapy

What cancer therapy usually involves stimulating host’s immune system to fight the cancer? It normally uses naturally occurring what? What are some examples?

immunotherapy—> normally uses cytokines like IFNs, or ILs

Many cancers appear to eliminated by surgery/radiation but then reoccur later. This implies that the primary tumor began to do what before it was removed? What are these called?

implies the tumor began to METASTASIZE before removed… these early metastases are called micrometastases

What is adjuvant therapy?

use of systemic agents to eradicate micrometastatic disease following localized modalities such as surgery, radiation, or both

What is neoadjuvant therapy? What is the goal?

drug therapy given PRE-OPERATIVELY, goal is to make other treatments more effective by reducing tumor burden AND to destroy micrometastases

Cancer chemotherapy may be indicated as…

a. primary

b. palliative

c. adjuvant

d. neoadjuvant

e. all of the above

e

Treatment with cytotoxic drugs is the primary curative modality for…

• hematological malignancies

• some solid tumors

Growth of most tumors is illustrated by the __________________ curve.

gompertzian tumor growth curve

The gompertzian tumor growth curve describes the relationship between what 2 things?

age and expected death

What are the steps of the cell cycle?

1. M: mitosis

2. G0 or G1: Gap 0 or Gap 1

3. S: DNA Synthesis

4. G2: Gap 2

What’s the difference between G0 and G1?

G0- “dormant phase” cell cycle stays dormant in this phase until it goes to G1

G1- “first gap phase” cell prepares for DNA synthesis

Some drugs effect particular phases of the cell cycle and are known as “cell-cycle phase-specific agents”. They are known as __________ dependent.

Schedule Dependent

Some drugs effect particular phases of the cell cycle and are known as “cell-cycle phase-specific agents”. What drugs exert their major effect on the S phase?

antimetabolites

Agents used in cancer chemotherapy are categorized by __________ or _________.

MOA or Origin

What do alkylating agents do?

exert effects on DNA and protein synthesis by binding to DNA and preventing the unwinding of the DNA molecule

For the following drug classes indicate if they are administered PO or IV?

• endocrine therapies —→

• monoclonal antibodies —→

• Targeted therapies —→

• Immunotherapies—→

• endocrine therapies —→ PO

• monoclonal antibodies —→ IV

• Targeted therapies —→ PO

• Immunotherapies—→ IV

What does the “RECIST” criteria stand for? What is measured at baseline and later?

• RECIST stands for Response Evaluation Criteria in Solid Tumors

• what is measured? overall tumor burden, measurable disease and target lesions

What are the 3 responses to chemotherapy and other treatment methods?

• complete response (CR)

• partial response (PR)

• progressive disease (PD)

What is complete response? (in terms of response criteria for solid tumors)

disappearance of ALL target lesions and lymph nodes are reduced to <10nm

What is partial response? (in terms of response criteria for solid tumors)

30% of greater decrease in the sum of diameters of target lesions from baseline

What is progressive disease? (in terms of response criteria for solid tumors)

• 20% of greater INCREASE in the sum of diameters of target lesions when compared to the smallest sum since treatment initiation

• development of 1+ new lesions

Responses in leukemias and multiple myeloma measured by elimination of ____________________.

abnormal cells

____________ hypothesis addresses issues of tumor cell heterogeneity and inevitable development of drug resistance.

Goldie-Coldman

BEFORE chemotherapy what should be each of the following lab values?

• ANC ≥___________ cells/mm³

• Platelets ≥__________cells/mm³

• ANC ≥ 1,500 cells/mm³

• Platelets ≥100,000 cells/mm³

Chemotherapy is generally dosed based on _______ or fixed dose and is administered in ________.

based on BSA and is administered in cycles

Chemotherapy cycles are usually ____ or ____ days long or every ___ or __ weeks.

Chemotherapy cycles are usually 21 or 28 days long or every 3 or 4 weeks.

Cytotoxic drugs are which of the following:

a. carcinogenic

b. mutagenic

c. teratogenic

d. all of the above

d

WHAT USP regulates the preparation and compounding of hazardous drugs?????

USP <800>

What are the 2 main clinical guidelines in oncology?

• American society of clinical oncology (ASCO)

• National Comprehensive cancer network (NCCN)