Personalised Medicine - Curing Cancer

Question 1

What is cancer?

Answer 1

A disease of population of cells that live, divide, invade and spread without regard to normal limits.

Question 2

With regards to cells what normally occurs?

Answer 2

Normally, cells growth, death and location are tightly regulated in the body

Question 3

On a molecular basis what causes cancer?

Answer 3

Cancer is a diseased caused by a mutation in DNA

Caused by exogenous carcinogens, DNA replication errors, inheritance

Question 4

What DNA genes are mutated that results in cancer?

Answer 4

Oncogenes (become acitvated)

Tumour suppressor genes (inactivated)

Question 5

With regards to cancer what may be suitable targets for drug therapy?

Answer 5

Cancer biomolecules maybe suitable as molecular targets for drug therapy

Question 6

How can cancer cells be distinguished from other cells/

Answer 6

Cells aquire a series of key phenotypic characterisitcs

Question 7

What are the key characteristics of cancer cells?

Answer 7

• Evading apoptosis
• Self-sufficiency in growth signals
• Insensitivity to antigrowth signals
• Sustained angiogenesis
• Limitless self replication potential
• Tissue invasion and metastasis

Question 8

Whats the three key points of the pathophysiological basis of cancer?

Answer 8

• Growth and invasion of primary tumours
• Metastasis and distant effects of wide spread disease
• Systemic effects of paraneoplastic syndromes

Question 9

How many people get cancer in NZ each year and how many die?

Answer 9

21050 new cases

8891 deaths

Question 10

What are the five most common cancers in NZ?

Answer 10

1) Prostate
2) Colon, rectum and anus
3) Breast
4) Melanoma of the skin
5) Trachea, bronchus and lung

Question 11

What is cancer chemotherapy?

Answer 11

The use of chemicals to kill cancer cells in the body

Question 12

What are some examples of chemotherapeutic agents?

Answer 12

• Metal complexes
• DNA binding molecules
• Vitamin mimics
• Antibodies

Question 13

How is cancer chemotherapy administered?

Answer 13

intravenously, then spreads systemically and kills cancer cells everywhere in the body

Question 14

How do cancer chemotherapies not kill normal cells?

Answer 14

They are selective for cancerous cells.

Selective toxicity is achieved through direct, metabolic, hormonal and immune cytotoxicity mechanisms

Question 15

When did cancer chemotherapy begin and describe the studies results?

Answer 15

1942, Goodman at yale used mustard gas derivative to treat lymph gland cancer, resulted in cancer regression

Important forerunner to modern alkylating agent i.e cyclophosphamide

Question 16

When did chemotherapy first cure cancer?

Answer 16

1958, Hertz, showed that methotrexate cured choriocarncinoma

Showed that chemotherapy could cure cancer

Question 17

When was the anticancer platinum complex discovered

Answer 17

1978 - Cisplatin, barnett showed that it acted on a range of solid tumors

Question 18

When did targeted therapies being to be used?

Answer 18

1998

Question 19

What is target therapies?

Answer 19

Therapeutic targeting of specific molecules involved in cancer development and progression

Question 20

What is targeted therapies potential?

Answer 20

Potential for more effective less toxic and individualised cancer therapies.

Question 21

What are two major landmarks in targeted therapies?

Answer 21

1998 - trastuzumab approved for HER-2 positive breast cancer

2001- Imatinib approved for chronic myelogenous leukemia

Question 22

What is chronic myelogenous leukaemia (CML)?

Answer 22

chronic myelogenous leukaemia the product of the acquisition of Philadelphia chromosome, abnormal fusino protein and self sufficiency of growth signals,

Question 23

What did treatment of CML with imatinib compared to other treatments do?

Answer 23

Resulted in 95% survival compared to next best of 40%

Question 24

What is the latest modern revelation of cancer therapy?

Answer 24

2011 - immune checkpoint modulation

Question 25

What is immune checkpoint modulation?

Answer 25

The use of monoclonal antibodies binding cytotoxic T lymphocyte antigen 4 i.e ipilimumab (CTLA-4) or Programmed death one i.e nivolumab (PD-1) to modulate the immune systems response to prevent cancer growth

Question 26

What do ipilimumab and nivolumab do?

Answer 26

• Supresses antitumour T-cell immune cytotoxicity

i. e Which decreases tumour growth

Question 27

What do results of ipilimumab and nivolumab use indicate?

Answer 27

Durable responses in subgroups of patients with melanoma, non-small lung cell cancer

But this immune suppression can result in

• Colitis
• Dermatitis
• Endocrinopathies

i.e immune related side effects

Question 28

What are some pharamcolgical anticancer treatment actions and side effects?

Answer 28

Anti-proliferation = Diarrhoea , alopecia
DNA mutagenesis = Cancer
Sex hormone defficiency = impotence
Blocked growth factor receptor signalling = Hypertension, clotting
Autoimmunity = colitis

Question 29

Can cancers be resistant to treatment?

Answer 29

Only if they acquire the appropriate mutations

Question 30

Whats the three summaries of this lecture?

Answer 30

• Targeted therapies inhibit oncoprotein drivers of cancer development and progression
• Individualisation of therapy by genetic testing to detect somatic mutations to direct patients to specified targeted therapies
• Adverse effects are often related to the main pharmacological mechanism.

Question 31

What are the stages of cancer?

Answer 31

1-5 where 5 has metastasized.