Tackling, treating and tending to tumours: top 5 significant (molecular) advances in cancer research

Posted by ap507 at May 05, 2016 04:30 PM |
PhD student Mohan Harihar explores five major developments in cancer research in the last few decades
Tackling, treating and tending to tumours: top 5 significant (molecular) advances in cancer research

Gleevec interacting with the tyrosine kinase

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There may not be a definitive ‘cure’, or set of cures, for cancer at present but the on-going fight has proven fruitful since research began. From the rudimentary use of radiation treatment in 1903 and advent of chemotherapy in 1949, to the new targeted therapies on the market, the seemingly ever-improving biomedical technology has led to more people beating cancer than ever before.

So how has this been achieved?

The most exciting ideas and research being conducted currently revolves around targeted therapies at the molecular level.

Due to the multifaceted nature of cancer there is still a necessity for further discoveries and targeted therapies to combat cancer.

Nonetheless the substantial progress in this area already should not be forgotten. That being said, here are my top five (molecular) cancer advances to-date.

1) The development of Trastuzumab (Herceptin) for treating breast cancer

Trastuzumab, or Herceptin as it is known on the market, is an example of a targeted drug that has been in use since 1998.

It is routinely given to patients with breast (and stomach) cancers where there are high levels of a particular protein called ‘human epidermal growth factor receptor 2’ (HER2) (referred to as HER2-positive cancers). HER2 acts as a docking site for another protein, or ‘growth factor’, and upon activation stimulates tumorous cell growth and division.

So why is this important?

According to the National Health Service approximately 1 in 5 cases of breast and stomach cancer are HER2-positive.

In this case Herceptin binds to the HER2 proteins and prevents their complementary growth factors from docking. By accomplishing this cells are prevented from growing and dividing.

Herceptin is used to treat early HER2-positive cancer following surgery and/or radiotherapy/chemotherapy by decreasing the risk of the cancer re-occurring. The drug may also be used to treat advanced metastatic (cancer which has spread to other body parts) HER2-positive breast and stomach cancers.

This has been a major breakthrough in cancer research and will continue to save and prolong the lives of many in the future.

2) The development of Imatinib (Gleevec) to combat chronic myelogenous leukaemia (CML)

Imatinib, commercially known as ‘Gleevec’, is another example of a targeted therapy and has been hailed as a ‘miracle drug’ since its approval in 2001. It has been notably used to treat a selection of leukaemias (cancer of the white blood cells).

Biochemically Gleevec is referred to as a ‘tyrosine kinase inhibitor’. Tyrosine kinases are proteins which cells often require for growth signalling. Therefore by inhibiting these proteins Gleevec can reduce the rate at which cells grow and divide.

One particular cancer, called ‘chronic myelogenous leukaemia’ (CML), can occur as a result of a genetic alteration leading to an abnormal hybrid protein known as ‘BCR-ABL’ being formed. This protein contains a tyrosine kinase which is permanently “switched-on” resulting in non-stop cell growth and division.

Gleevec is able to address this issue by binding near the active portion of the tyrosine kinase and reducing its activity by hindering a key interaction between the tyrosine kinase and its target molecule.

3) The development of the HPV-induced cervical cancer vaccines Gardasil and Cervarix

Prevention is always better than cure.

Cervical cancer is the second most common cancer in women below the age of 35 according to Cancer Research UK. Approximately 3060 women are diagnosed with cervical cancer in the UK every year.

The human papillomavirus (HPV) is a virus which can be responsible for a number of physical ailments – one of which is cervical cancer. In some cases HPV will not be eradicated by the body’s immune system,

HPV vaccine, Gardasil
HPV vaccine, Gardasil
and over time can induce cellular changes which increase the probability of a normal cell becoming cancerous.

In most cases cervical cancer occurs in patients who have had exposure to a particular category of HPVs known as ‘high-risk HPVs’.

Following a series of clinical trials and a report published in 2005, Gardasil was revealed to fight against certain types of high-risk HPVs responsible for causing cancer. In 2006 Gardasil became licensed in the UK for females between the ages of 9 and 26.

In 2007 a new vaccine, Cervarix, also become licensed in the UK for administering to females aged 10 and 25.

Today the UK has in place a national screening and vaccination program aimed at girls in secondary education.

4) The discovery of the breast cancer genes BRCA1 and BRCA2

Another instance where prevention, in some cases, has been better than cure.

BRCA1 and BRCA2 are two genes (‘pockets’ of instructions within DNA needed for protein production) which normally inform cells to repair DNA damage. Faulty versions of these genes mean an individual is less likely to repair such damage, ultimately putting them at a higher risk of developing cancer.

Cancer Research UK states the average UK woman has a 12.5% chance of developing breast cancer – this percentage rises to 60-90% when a faulty BRCA1 gene is present.

However only about 5% of breast cancer cases overall involve faults in genes such as BRCA1.

Due to this observation many argue the discoveries of the genes BRCA1 and BRCA2 (in 1994 and 1995 respectively) have not been as impactful as other breakthroughs. Nevertheless from a scientist’s point of view the thrill of this particular development comes from not solely being able to target these genes therapeutically but from the ability to discover such genes which pre-dispose an individual to cancer.

5) The field of ‘immunotherapy’

Perhaps the most promising breakthrough in the fight against cancer has been the field of ‘immunotherapy’. Immunotherapy can be best described as ‘awakening’ a person’s immune system to fight cancer cells. Whilst this is still a growing field the potential is staggering.

Multiple cancer treatments have benefited hugely from immunotherapy – including bladder, brain, breast, colorectal, melanoma, prostate and pancreatic cancers.

One major attraction of this area is that engaging the immune system could, in theory, mean long-term benefits. The immune system can retain a degree of ‘memory’ when fighting diseases. Therefore in cases where patients experience a re-occurrence of a treated cancer, the immune system could tackle this problem without additional prompting.

Tumour-infiltrating lymphocytes in a colorectal cancer
Tumour-infiltrating lymphocytes in a colorectal cancer

One particular approach in this field involves the use of ‘immune checkpoint modulators’ – drugs which can control the strength and duration of the immune response.  Two drugs of this nature which have been instrumental in addressing advanced melanomas (skin cancer) and lung cancers include ‘iplimumab’ and ‘nivolumab’.

Another technique involves artificially growing, in a laboratory, a type of immune cell, called a ‘tumour-infiltrating lymphocytes (TILs)’, which naturally attack cancer cells. These are then re-introduced into the patient with the cancer – a process called ‘adoptive cell transfer’.

This aims to strengthen the already existing immune response which may have been suppressed by the tumour itself.

In addition to the techniques mentioned previously, therapeutic vaccines have also been at the vanguard of certain cancer treatments.

For all these reasons, immunotherapy has revolutionized cancer treatment.

All in all the future looks bright for cancer research with the sharpest minds continuing to harness state-of-the-art technology to make breakthroughs. It is therefore the hope that we can one day definitively progress from targeted treatments to targeted ‘cures’.

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