CANCER TREATMENT IS GETTING PERSONAL.CANCER TREATMENT IS GETTING PERSONAL.

Introduction

Over the last 40 years, cancer survival has doubled in the UK.¹ A cancer diagnosis comes with a plethora of anxieties, largely centred around invasive treatment options; 45% of patients diagnosed with cancer have surgery to remove the tumour, 27% have radiotherapy, and 28% have chemotherapy.¹ Whilst these treatments are largely successful, they come with many debilitating side effects, including pain, hair loss, fatigue, and emotional effects.²

Cancers are hugely complex diseases, with an array of genetic, environmental and molecular factors at play.³ Furthermore, the tumour environment is prone to change as the cancer develops, meaning the goal post moves throughout treatment.³ With this in mind, is a one-size-fits-all approach appropriate for cancers?

Personalised medicine, also referred to as precision medicine, is a branch of therapeutics which focuses on tailoring treatments to individuals. This has vast potential in enabling earlier diagnosis, risk assessment, and optimising treatment.⁴ Continuing with the oncology article series, we will delve into how personalised therapy is being adopted in cancer technologies so far.

ChemoID

ChemoID is a novel technology helping doctors make more educated decisions regarding the chemotherapy agent(s) used to treat their patients.⁵ Using a small biopsy, tumour cells can be grown in culture and treated with FDA-approved chemotherapy drugs to identify which agent(s) kill not only the tumour cells, but also the cancer stem cells (CSCs) known to cause relapse, most effectively.⁵ Targeting of CSCs as well as the bulk of the tumour cells is a novel paradigm in the realm of cancer treatment, and drastically decreases the probability of relapse.⁵ Furthermore, ChemoID increases accuracy of treatment, and decreases toxicity side effects and stress to the patient by eliminating unnecessary chemotherapy courses.⁵

Intensity-Modulated Radiotherapy (IMRT)

Radiotherapy uses high doses of radiation to kill cancer cells and shrink tumours.⁶ This inadvertently leads to damage of neighbouring healthy cells, leading to a wide range of negative side effects.⁶ IMRT provides a solution to this by allowing more accurate targeting of the radiation dose to the tumour itself, thereby reducing the harmful side effects of traditional radiotherapy.⁷ The technique uses computer-controlled linear accelerators to deliver precise radiation doses to the tumour site.⁷ Prior to treatment, the tumour is mapped using computed tomography and magnetic resonance imaging, and doses are calculated to determine the dose intensity pattern most appropriate for the tumour.⁷ This technique allows the radiologist to control the intensity of the radiation to fit the size and shape of the tumour, while limiting exposure to surrounding cells.⁷ This reduces treatment toxicity and leads to fewer side effects than traditional radiation techniques; however, at present involves much longer treatment times and safety checks prior to treatment.⁷

Next-Generation Sequencing (NGS)

NGS, discovered in the early 2000s,⁸ is a revolutionary DNA sequencing technique which allows sequencing of an entire human genome in just one day - the previous technology, Sanger sequencing, required over a decade to deliver the same output.⁸ As a result, NGS has proved invaluable in progressing numerous areas of clinical science, including personalised medicine for cancer therapeutics. NGS can be used to identify novel and rare cancer mutations, detect carriers of mutations, and provide valuable insights for targeted therapy.⁹ This technique has uncovered novel mutations for several cancers, including bladder cancer,¹⁰ renal cell carcinoma,¹¹ and small-cell lung cancer.¹² This has shed further light on the mechanisms of tumourigenesis, in turn identifying potential therapeutic targets.⁹

NGS also provides opportunities in the field of genetic testing for cancer. It is estimated that 5–10% of cancers are hereditary.⁹ To date, Sanger sequencing has been the most widely used technology for genetic testing, which is a time consuming, expensive and labour intensive process.⁹ Applying NGS to this practice would deliver higher throughput and shorter wait times.⁹ Some studies have tested the application of NGS in this way, and in some cases identified mutations which were not previously picked up by Sanger sequencing.^13,14,15,16

Arguably the most exciting use of NGS in cancer therapeutics is its promise in personalised medicine. NGS for personalised medicine is in its naïve stages of development; however has been used in the treatment of pancreatic cancer,¹⁷ non-small cell lung cancer,¹⁸ and promyelocytic leukaemia,¹¹ among others.⁹ One particularly moving case involved genetic researchers at Washington University using NGS to sequence the genome of a colleague in their team who had adult acute lymphoblastic leukaemia.¹⁹ Following a 10-year long battle with two relapses and exhausting all conventional therapies, the researcher’s colleagues identified unusual activity in a non-mutated gene FLT3 through RNA sequencing.¹⁹ The drug sunitinib, approved for treatment of renal cancer, is known to inhibit FLT3.¹⁹ Applying the results of the RNA sequencing to treat the researcher with sunitinib, the researcher’s blood samples showed no leukaemic cells present and just two weeks later, indicated that his leukaemia was in remission.¹⁹

Conclusion

Cancer is a complex disease with a vast array of factors coming into play. For this reason, personalised therapeutics offer great promise in the future of cancer therapeutics. However, the additional upfront costs implicated in these types of therapy currently still present a barrier to their wider use. Additionally, the datasets for patients undergoing personalised therapy remains too small to determine whether the cost saving of avoiding unsuccessful therapy offsets the increased upfront costs.²⁰ Furthermore, personalised therapy is often more labour intensive and requires a higher degree of specialism than conventional treatments.²⁰

Whilst we are not yet at the point of personalised medicine being fully integrated into cancer treatment, we can confidently say that it has much to offer in the future.²⁰ At TVF we are passionate about keeping up-to-date with the latest innovations in healthcare, so we can make informed strategic decisions to benefit your team. To find out more about how we can support you, get in touch.

By Liz Ford