Lecture 2 - Cancer development and therapeutic differentials

Question 1

Describe benign tumours.

Answer 1

In benign tumours, cells are not cancerous and won’t spread. slow growth rate, slight vascularity, rarely recurs after removal, necrosis and ulceration is unusual, systemic effects are unusual unless the tumour is a secreting endocrine neoplasm.

Question 2

Describe malignant tumours

Answer 2

In malignant tumours, cells are cancerous and can spread to other tissues and organs. rapid growth rate, moderate marked vascualirt, frequently recurs after removal, necrosis and ulceration common, systemic effects are common and usually life threatening.

cancerous or malignant cells have a large number of irregular shaped dividing cells large variably shaped nuclei, small cytoplasmic volume relative to nuclei, variation in cell size and shape, loss of normal specialised cell features, disorganised arrangement of cells and poorly defined tumour boundary.

Question 3

what is tumour grade?

Answer 3

grade 1 - well differentiated
grade 2 - moderately differentiated
grade 3 - poorly differentiated
grade 4 - undifferentiated

different tumour staging for different cancers eg Gleason staging system for prostate cancer and TNM system for breast cancer.

overall based on the degree of differentiation, spread, size, organisation of tumour.

Question 4

what differentiates being from malignant tumours?

Answer 4

Nearly all benign tumours grow as cohesive, expansive masses. The growth of malignant cancers is accompanied by progressive infiltration, invasion and destruction of the surrounding tissue
Next to the development of metastases, invasiveness is the most reliable feature that differentiates malignant from benign tumours.

Question 5

what is metastasis?

Answer 5

metastases are tumours that refer to the spread of cancer cells from the original or primary tumor to other parts of the body.

Metastasis marks a tumour as malignant as benign neoplasms do not metastasise. They penetrate into blood vessels, lymphatics and body cavities.

Question 6

what are exceptions to the statement that all cancer can metastasise?

Answer 6

Exceptions are neoplasms of the glial cells in the central nervous system, called gliomas, and basal cell carcinomas of the skin. Both are highly invasive forms of neoplasia but they rarely metastasise.

Question 7

what is the likelihood of a tumour to metastasise?

Answer 7

The more aggressive, the more rapidly growing, and the larger the primary neoplasm, the greater is the likelihood that it will metastasise or has already done so.

Question 8

what are the stages in formation of metastases?

Answer 8

capillaries grow into cancer -angiogenesis,

malignant cell breaks down intercellular matrix (capillaries within neoplasm),

malignant cell enter the capillary and malignant cells circulate round body in blood.

malignant cell adheres to blood vessel wall, travel into tissue t new site and malignant cell divided to form matasatises at new site

Question 9

what are different cancer types?

Answer 9

leukemias are cancers of he blood or bone marrow

sarcomas are cancers of the connective or supportive tissue (bone, cartilage, fat, muscle, blood vessels) and soft tissue - rarer

carcinomas are cancers that arises from epithelial cells. the include breast, liver, lung, and stomach etc

Question 10

what were cancer treatment strategies before vs now?

Answer 10

Surgery and/or radiotherapy accompanied by chemotherapy/immunotherapy etc

now we use surgeries, radiation therapies, chemo therapy, immunotherapy, hormone therapy, targeted therapy and stem cell therapy

Question 11

what is the aim for designing cancer drugs and what aspects of the cells can we investigate?

Answer 11

Focus to design cancer drugs is to find difference between cancer and normal cells, so we can target the cancer. In cancer cells, we can investigate to target metastasis, angiogenesis, antigens expressed, and also the rate of growth as cancer cells divide faster than normal cells.

Question 12

what is the main goal of antineoplastic agents?

Answer 12

to eliminate the cancer cells without affecting normal tissues. in reality all cytotoxic drugs affect normal tissue as well as malignancies. aim for a favourable therapeutic index.

therpaueitc index = LD50/ED50

Question 13

describe the cell cycle.

Answer 13

the cell cycle regulates growth and division
G1 - cell increases in size, produce RNA and synthesises proteins. cells can go into G0 where they no longer divide. this is reversible stage

S - synthesis phase. DNA replication takes palce

G2 - cell will continue to grow and produce new proteins required for cell division

M - mitosis - point in the cell cycle where cell divides in two.

Question 14

what controls the cell cycle?

Answer 14

Cyclins are the proteins which control the progression through the cell cycle,
Each gets turned on when required to allow progression through next phase

Question 15

what are cyclin dependant kinases?

Answer 15

cyclins bind to CDKs activating the CDKSs to phosphorylate other molecules. Cdks signal to the cell that it is ready to pass into the next stage of the cell cycle

Question 16

what are Cdks controlled by?

Answer 16

CDKs are controlled by inhibitors of the cell cycle (many of these are tumour suppressor genes such as P21)

which are in turn controlled by oncogenes and tumour suppressor genes such as p53 which is a protein that regulates the cell cycle and hence functions as a tumour suppressor

Question 17

what are cell cycle checkpoints?

Answer 17

Points at which cell checks on DNA damage and chromosome alignment whether it is Ok. if it is not ok, then cells will arrest at these points. cells either repair or die.

In cancer cells often repaired but repair is faulty then cells progress and divide > genomic instability and mutation
Arrest is controlled by tumour suppressors p53 and pRB

Question 18

what do cancer treatments drugs do?

Answer 18

cancer treatments include drugs drugs that can stop cancer cells from dividing and therefore induce apoptosis. as cancer cells divide more than normal cells this gives a therapeutic differential.

Question 19

what happens to the cells cycle checkpoints in cancer cells?

Answer 19

in cancer cells many of these control proteins are broken or deleted thus cancer is essentially a loss of cell growth and failure of the body to detect dangerous mutated cells and kill them.