Cancer

Question 1

What is cancer?

Answer 1

Cancer is a disease in which cells within the body proliferate uncontrollably and in some cases invade and destroy healthy surrounding tissue via metastasis.

Question 2

What are the key features of cancer?

Answer 2

Cancer cells are immortal, stimulate angiogenesis, do not differentiate into cell types, (bind to, digest, and cross basal membrane to spread), ignore stop signals by local normal cells, etc…

Question 3

How does cancer typically progress?

Answer 3

Cancer is localized -> cancer grown but not spread -> cancer grown larger and spread to lymph -> cancer invades other tissue and organs.

Question 4

What are the cancer cell changes that may occur?

Answer 4

Aplasia; failure of an organ/tissue to develop or function normally (absence of growth)
Hypoplasia;partial growth (with loss of function)
Atrophy; partial or complete wasting
Hypertrophy; cells increase in size
Hyperplasia; cells increase in number
Metaplasia; replacement of mature cells with less specialized cells
Dysplasia; replacement of mature cells with immature cells.

Question 5

What are the main methods of cancer diagnosis? Outline how.

Answer 5

Radiological; radiological imaging of masses
Cytological; evaluation of cells under microscope
Histological; evaluation of tissue under microscope

Question 6

What are the main causes of cancer? Both external and internal causes.

Answer 6

External; carcinogens(smoke, asbestos, etc..), viruses(links between HPV and cervical cancer), and radiation(UV rays can case malignant melanoma)
Internal; some cancers are inherited or caused by genetic mutations (i.e. typically mutations in more than one gene are required for cancer to develop, these genes are usually cell growth promoting genes(proto-oncogenes) and tumour suppressor genes(growth inhibitors))

Question 7

What are the main treatments of cancer?

Answer 7

Surgery(only if operable), chemotherapy(effective but also impacts other cells), radiotherapy(effects are greater on rapidly dividing cells), etc..

Question 8

How are malignant and benign neoplasms different histopathologically?

Answer 8

Benign; tumours are encapsulated cell masses that do not invade local tissue, metastasize, or become lethal. (Visual; distinct, smooth, regular borders)
Malignant; tumours are cell that can invade local tissue, metastasize, invade vital organs, become lethal. (Visual; irregular borders, fast growing)

Question 9

What are the characteristics of cancer cells?

Answer 9

Large variably shaped nuclei, many dividing cells, loss of normal features, variation of size, etc..

Question 10

What are some cancer classifications?

Answer 10

Carcinoma; epithelial glandular tissue
Sarcoma; connective tissue
Lymphoma; lymph 
Mesothelioma; skin/body lining cavity 
Glioma; neuroglial cells

Question 11

What metabolic process/effect do most cancer utilise? Describe the process.

Answer 11

Most cancers and cancer cells utilise the warburg effect, otherwise known as aerobic glycolysis.

Question 12

How does cancer metastasise? Outline.

Answer 12

Metastasis occurs once cells break off from the primary tumor and travel through the body growing in other areas. This usually occurs when tumor cells circulate in the blood or lymph system then sticks to the vessel walls and seep into another body tissue and grow.

Question 13

What are the steps of metastasis?

Answer 13

Local invasion; through basement membrane into ECM.
Intravasion; through walls of lymph and vessels.
Circulation; tumor cells migrate via lymph system or blood system.
Arrest, adhesion, & extravasion; migrate into surrounding tissue.
Proliferation; cells multiply forming small tumors (micrometastases).
Aniogenesis; micrometastases stimulate growth of new blood vessels to bring oxygen and nutrients.

Question 14

How are pro-oncogenes related to cancer progression?

Answer 14

Pro-oncogenes are normal cell growth promotors however in cancer these pro-oncogenes transition into oncogenes due to mutations. Oncogenes cause increased stimulants of cell division, inhibit differentiation, and halt cell death resulting in uncontrolled cell growth.

Question 15

What are the 2 types of ‘Tumour Suppressor Genes’ and their respective roles?

Answer 15

Brakes; genes the code for proteins to halt cell division (mutations in these genes cause loss of function [e.g. p53]). P53 determines whether a damaged cell lives or dies, as a result, it keeps cells healthy and cancer free. (Half of all human cancer have p53 off.)
Caretakers; genes the code for proteins to repair damaged DNA (e.g. BRCA1 genes). Mutations in these genes DON’T cause cancer but make the frequency of other mutations increase with faulty repair mechanisms which allows cancer risk to increase.

Question 16

What receptors, proteins, and factors are increasingly expressed in cancer and what are the effects?

Answer 16

VEGF; is a mediator of angiogenesis in cancer, in which it is upregulated by oncogene expression to allow the cancer to grow.
TGF-Beta; is known to suppress the immune system by inhibiting NK-cells, etc… Therefore, the cancer increasing expression of this protein leads to the suppression of the immune system allowing the cancer to grow whilst avoiding destruction.

Question 17

What is CSCT and the 2 main theories?

Answer 17

CSCT proposes that there exists a sub-population of cells called cancer steam cells that multiply indefinitely, are resistant to chemo, and are responsible for relapses.
The 2 main theories include:
Stochastic model; growth is random to which all tumor cells can contribute.
CSCT; suggest a clear hierarchy of cells within a tumor.

Question 18

What is aneuploidy? And its effects on cancer progression?

Answer 18

Aneuploidy is the presence of an abnormal number of chromosomes in a cell(e.g. having 45 instead of 46 chromosomes). Extra doses of genes are associated with disruption of normal DNA action and cell control hence malignancy.

Question 19

What is telomeres? And its effects on cancer progression?

Answer 19

Telomeres are DNA segments that cap ends of chromosomes(they shrink every cell division). In cancer cells, an enzyme ‘telomerase’ is produced and some cancers can employ lengthening of telomeres. Bothe of these mechanisms elongate and replace telomere sections effectively making the cell immortal.

Question 20

What is cachexia? And its effects on cancer progression?

Answer 20

Cachexia is the weakness and wasting of the body due to severe chronic illness. This is due to a key feature of cancer: upregulation of glycolysis and aerobic ATP production via lactic acid(Warburg effect). As a result, other tissues are starved of energy, patients are fatigued and experiencing cachexia, etc…

Question 21

What is EMT(detail the process)and it’s importance in cancer?

Answer 21

Epithelial to mesenchymal transition plays a crucial role in the process of metastasis in some cancers.

Question 22

What are some symptoms of cancer?

Answer 22

Bone pain, jaundice(cancer spread to liver), CNS changes(cancer spread to brain), weight loss, fatigue, etc..

Question 23

Describe the Warburg effect.

Answer 23

Despite cancer cells being in an aerobic environment, they will perform aerobic glycolysis rather than oxidative phosphorylation(blocked). (Glucose is taken in -> glycolysis -> pyruvate -> lactate[2 ATP/mol]) THIS IS KNOWN TO BE VERY INEFFICIENT.