Targeted therapies – the next step forward for cancer treatment?

Author: Professor Gareth Williams, molecular pathologist and medical director of Oncologica UK.

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It is fair to say that until now, chemotherapy has led the way in cancer treatment within the UK, however this is rarely without side effects. Extensive research and modern technology has led to alternative treatment options for cancer known as targeted therapies. But what are the advantages of targeted therapies over chemotherapy and how can a doctor know which targeted therapy to use to treat an individual patient’s cancer?

Professor Gareth Williams, molecular pathologist and medical director of Oncologica UK discusses how genetic profiling can help doctors to pinpoint the best treatment for an individual patient’s cancer.

The incidence of cancer in the UK is on the rise. Since the early 1990s, incidence rates for all cancers increased by 13%. Furthermore, half of all cancers in England are diagnosed at a late stage. With this in mind, effective treatment is more important than ever. Until now, chemotherapy has often been the go-to treatment option and while this remains an important treatment for cancer, it is certainly not the best solution for all tumours. Indeed, chemotherapy does not come without difficulties so other, more modern treatments are always worth considering.

Targeted cancer therapies are the cornerstone of personalised medicine, a form of medicine that uses information about a person’s DNA profile to treat cancer. There are in fact, hundreds of targeted therapy options potentially available. However, that coupled with the fact that there are several hundred different cancers, each with different genetic mutations, means it is a difficult task for a doctor to pinpoint exactly which treatment option is best for which cancer. Therefore, even for an experienced oncologist, there are major challenges in identifying the most effective drug combinations, particularly for patients with advanced disease who have not responded to standard protocols. 

Genetic testing

Recent advances in genomic science, however, are making it possible for doctors to identify, with a greater level of accuracy, exactly which drugs are best to treat the cancer of an individual patient. Genomic tests can precisely identify the most effective drug in over 90%1 of patients. Each tumour is unique and will have its own genetic mutations. By carrying out testing which analyses a tumour’s DNA and RNA, a doctor can see its genetic profile. This can then be mapped to anti-cancer targeted therapies to see which therapy is right for the individual tumour. This can dramatically increase the success rate of treating advanced cancers.

Targeted therapies versus chemotherapy

Although chemotherapy does continue to have its place in cancer treatment, it is often not without traumatic side effects for patients. Chemotherapy drugs target cellular mechanisms common to both cancerous and healthy cells. Drugs such as 5-Fluorouracil, Gemcitabine and Methotrexate disrupt DNA duplication while taxanes and vinca alkaloids block cell division. Although cell division occurs in cancer, normal tissues of the body also undergo cell division particularly those tissues with rapid cell turnover such as the gastrointestinal tract, skin and the haemopoietic system. Effectively chemotherapy drugs attack healthy cells as well as the mutated cancerous cells. This results in many of the serious side effects often associated with chemotherapy, such as hair loss, vomiting and infections. It also means that patients are often unable to take a dose of a drug high enough to fight the cancer effectively as their body simply cannot handle the damage the chemotherapy is doing to healthy cells.

In recent years, major advances have been made in the understanding of the molecular biological mechanisms that drive cancer cells to proliferate and spread, which has led to the development of ‘magic bullets’ – drugs that target the mutations present in cancer cells but leave normal cells undisturbed. Many cancer genes have been identified that cause tumours to grow through abrogation of a wide range of processes such as accelerated cell proliferation, inducing instability of the cells genome, increased propensity to spread to distant sites called metastasis and more recently disruption of the immune system. These cancer genes are activated by mutations and these mutations are only present in cancerous cells. One such drug, Trastuzumab (Herceptin) targets the HER2 gene and is licensed for breast and gastric cancers, while drugs such as Gefitinib, Erlotinib and Afatinib are used in the treatment of lung cancers with mutations in the EGFR gene.

Furthermore, while the majority of chemotherapeutic drugs are given in hospital by infusion, targeted therapies have the advantage of being administered orally.

Chemotherapy is still a treatment option for fighting cancer. However, with new scientific advances leading to tests which can better establish the best treatment to treat the individual, it is something all doctors should be aware of.

Reference

  1. UKAS accreditation monitoring of Oncofocus test (www.oncologica.com/oncofocus) for ISO15189:2012.

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