Flashcards in Personalised Medicine - Curing Cancer Deck (31):
What is cancer?
A disease of population of cells that live, divide, invade and spread without regard to normal limits.
With regards to cells what normally occurs?
Normally, cells growth, death and location are tightly regulated in the body
On a molecular basis what causes cancer?
Cancer is a diseased caused by a mutation in DNA
Caused by exogenous carcinogens, DNA replication errors, inheritance
What DNA genes are mutated that results in cancer?
Oncogenes (become acitvated)
Tumour suppressor genes (inactivated)
With regards to cancer what may be suitable targets for drug therapy?
Cancer biomolecules maybe suitable as molecular targets for drug therapy
How can cancer cells be distinguished from other cells/
Cells aquire a series of key phenotypic characterisitcs
What are the key characteristics of cancer cells?
- Evading apoptosis
- Self-sufficiency in growth signals
- Insensitivity to antigrowth signals
- Sustained angiogenesis
- Limitless self replication potential
- Tissue invasion and metastasis
Whats the three key points of the pathophysiological basis of cancer?
- Growth and invasion of primary tumours
- Metastasis and distant effects of wide spread disease
- Systemic effects of paraneoplastic syndromes
How many people get cancer in NZ each year and how many die?
21050 new cases
What are the five most common cancers in NZ?
2) Colon, rectum and anus
4) Melanoma of the skin
5) Trachea, bronchus and lung
What is cancer chemotherapy?
The use of chemicals to kill cancer cells in the body
What are some examples of chemotherapeutic agents?
- Metal complexes
- DNA binding molecules
- Vitamin mimics
How is cancer chemotherapy administered?
intravenously, then spreads systemically and kills cancer cells everywhere in the body
How do cancer chemotherapies not kill normal cells?
They are selective for cancerous cells.
Selective toxicity is achieved through direct, metabolic, hormonal and immune cytotoxicity mechanisms
When did cancer chemotherapy begin and describe the studies results?
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
When did chemotherapy first cure cancer?
1958, Hertz, showed that methotrexate cured choriocarncinoma
Showed that chemotherapy could cure cancer
When was the anticancer platinum complex discovered
1978 - Cisplatin, barnett showed that it acted on a range of solid tumors
When did targeted therapies being to be used?
What is target therapies?
Therapeutic targeting of specific molecules involved in cancer development and progression
What is targeted therapies potential?
Potential for more effective less toxic and individualised cancer therapies.
What are two major landmarks in targeted therapies?
1998 - trastuzumab approved for HER-2 positive breast cancer
2001- Imatinib approved for chronic myelogenous leukemia
What is chronic myelogenous leukaemia (CML)?
chronic myelogenous leukaemia the product of the acquisition of Philadelphia chromosome, abnormal fusino protein and self sufficiency of growth signals,
What did treatment of CML with imatinib compared to other treatments do?
Resulted in 95% survival compared to next best of 40%
What is the latest modern revelation of cancer therapy?
2011 - immune checkpoint modulation
What is immune checkpoint modulation?
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
What do ipilimumab and nivolumab do?
- Supresses antitumour T-cell immune cytotoxicity
i.e Which decreases tumour growth
What do results of ipilimumab and nivolumab use indicate?
Durable responses in subgroups of patients with melanoma, non-small lung cell cancer
But this immune suppression can result in
i.e immune related side effects
What are some pharamcolgical anticancer treatment actions and side effects?
Anti-proliferation = Diarrhoea , alopecia
DNA mutagenesis = Cancer
Sex hormone defficiency = impotence
Blocked growth factor receptor signalling = Hypertension, clotting
Autoimmunity = colitis
Can cancers be resistant to treatment?
Only if they acquire the appropriate mutations
Whats the three summaries of this lecture?
- 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.