02:05pm Sunday 24 September 2017

Individualised cancer treatment in sight

A biomarker is a measurable characteristic or substance which can be used as an indicator of some biological state or mechanism. Biomarkers are often evaluated to examine normal biological processes, pathologic processes, or bodily responses to therapy. A tissue or blood sample may contain molecular biomarkers indicating the presence of cancer and its severity.

Magnetic resonance imaging (MRI) can also be considered a type of biomarker, as the tumour in the image signals cancerous changes. But rarely do current biomarkers provide enough information to predict the treatment to which a patient will best respond.

This is precisely what the CCBIO research plan seeks to address by finding new biomarkers that will indicate which treatment is best suited to each cancer patient. Researchers at the centre will primarily be searching for markers by studying the tumour microenvironment, i.e. the cancer cells and their immediate surroundings.

Photo: Gades institutt/UiB SPREADING THE DAMAGE: A cancerous tumour (cancer cells in blue) has established an active microenvironment with profuse growth of blood vessels (angiogenesis, in red). This environment stimulates growth of the tumour and raises the risk of metastasis to other parts of the body. (Photo: Gades institutt/UiB)

Treatment does not help everyone

The development of ipilimumab, a drug that can extend the life of certain patients with metastatic malignant melanoma, illustrates the need for predictive biomarkers. A heated media debate erupted in Norway last year when the Norwegian Directorate of Health did not approve the medication for the national health care plan, only to be overruled by the Minister of Health and Care Services.

The dilemma is that the medication is only effective in 10–15 per cent of melanoma patients – and physicians currently have no way of knowing which patients those may be. Thus, for the vast majority of patients, the treatment leads only to false hopes and needless side effects, while society carries the brunt of the drug’s high cost (NOK 850 000 per patient per year).

“This is just one of many examples,” explains CCBIO director Lars A. Akslen. “Imagine what we could spare patients and society in terms of discomfort and expenditures if we could identify beforehand which patients would benefit from a medicine! It becomes clearer every day that biomarkers are the key to making that scenario a reality.”

Dr Akslen brings up example in which a biomarker has been successfully identified for changes in the HER2 gene in women with breast cancer. This gene codes for a protein that resides on cell surfaces and stimulates increased cell growth, making the cancer more aggressive.

From tissue samples, pathologists can identify the roughly 15 per cent of patients with HER2-positive breast cancer and administer the medicine Herceptin. In this case the biomarker and target for treatment are the same molecule; the medicine binds to the HER2 protein, inhibiting its function.

Thousands of biomarkers remain to be discovered – and until these are identified, physicians have no choice but to use treatment methods akin to firing a shotgun in the general direction of a target.

Photo: Kim E. Andreassen, UiB Lars A. Akslen (Photo: Kim E. Andreassen, UiB)

Predictive biomarkers should be required

“In my opinion,” asserts Dr Akslen, “the medical authorities should probably not approve new cancer medicines without a predictive biomarker. We need stricter requirements for cancer treatments to be more specifically targeted.” He adds that the pharmaceutical industry tends to be disinclined to cooperate on the research and testing of potential biomarkers.

Cells in aggressive cancer tumours share certain characteristics: the cells divide frequently while fewer than normal die; the cells secrete substances that stimulate blood vessel formation, supplying the tumour with blood and thereby oxygen and energy for further growth; the cells invade surrounding tissue and may enter the bloodstream to be transported to another site in the body and form metastatic tumours.

Dr Akslen will also study the cancer microenvironment. “I want to know the actual relationships within the tumour biology. What are the interactions between cancer cells and the microenvironment that surrounds them, such as blood vessels and connective tissue, and what does it all mean for a cancer’s aggressiveness?”

From lab research to patient treatment

One of the CCBIO centre’s strengths is that its activities encompass the entire value chain from basic to applied research. Research activities will enhance biological understanding of interactions within the tumour microenvironment, find new biomarkers and translate them to clinical implementation. The ultimate goal is to identify the right patients and provide individualised treatment.

Research on medical ethics and health economics is also an integral part of CCBIO activities. Several projects will focus on identifying the mechanisms that determine priorities in current cancer treatment.

Dr Akslen is himself a researcher at the Gade Institute in Bergen, a pathology-oriented institute which has been storing tissue samples from thousands of cancerous tumours since 1912. The CCBIO will identify new biomarkers using the abundance of information obtainable from these samples and other biological material in more recently established biobanks, and from patient histories and health registry data. The centre collaborates with a number of international partners positioned at the forefront of this research field.

The CCBIO has already patented and licensed three new biomarkers, one of them for the US market. The first new diagnostic markers are planned to be used clinically within 3–5 years, and a new clinical study will be initiated within three years.

Centre for Cancer Biomarkers (CCBIO)
  • Objective: To discover, validate and translate new cancer biomarkers to enhance biological understanding of cancer, ensure early diagnosis of aggressive cancers and develop more targeted treatment.
  • Centre director: Lars A. Akslen 
  • Partners: Biobank Norway, the Cancer Registry of Norway, the Tromsø Study, the Nord-Trøndelag Health Study (HUNT), MoMaTEC study group, BerGenBio AS, Harvard Medical School, and a number of individual researchers at European, US and Canadian universities. 
  • Annual allocation from the Research Council: NOK 17 million
  •  Total person-years: 50–60 persons 
  • No. of doctoral degrees planned: roughly 30

www.uib.no/ccbio

 

 

Written by:
Ingvill Bjørnæs/Else Lie. Translation: Darren McKellep/Carol B. Eckmann

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