Theme leader: Mara Martin Alonso

Colorectal cancer (CRC) is an abnormal growth in the colon or rectum that has the capability to invade and spread to other parts of the body.

CRC is the third most common cancer world-wide. In Norway it is the second most common cancer, affecting about 7% of the population, with 4602 new cases in 2018. Four out of ten people who develop CRC die of the disease within five years.

The chances of survival depend largely on the patient’s health, how advanced the cancer is at diagnosis, and whether the cancer can be surgically removed. The survival rate of CRC is high (>90%) when the cancer is detected at an early stage, but the cancer is often asymptomatic in the early phases. Early detection relies on good strategies for early detection, such as identifying and screening high-risk groups for CRC, in addition to population-based screening programs.

This theme focuses on understanding how CRC tumors develop and on identifying important genetic and epigenetic risk factors for CRC. An important aim is to identify novel biomarkers for early detection of CRC that can be measured easily and efficiently in patient samples. The methods used to investigate these factors include studying blood and tissue samples from clinical and population-based biobanks, as well as in vivo mouse models and in vitro cell and organoid models.

Aims

1. Identify novel risk factors for hereditary CRC
2. Identify small RNAs in blood that predict CRC diagnosis and progression
3. Investigate if circulating tumor DNA in the blood can accurately predict CRC diagnosis
4. Identify prognostic biomarkers in metastatic CRC from patient serum and tissue material
5. Gain new insight into epigenetic factors that control the initiation and early development of CRC
6. Determine the role of muscle cells in controlling (cancer) stem cells and the development of CRC

7. Characterize tumour heterogeneity within primary tumours and investigate how local properties may determine the tumour’s biology

Contact

Menno Oudhoff, Researcher

Theme leader: Eva Hofsli

A variety of treatments are available to help control cancer progression, including surgery, radiation therapy and drug treatments such as chemotherapy, targeted therapy and immunotherapy.

Treatment is however complicated because CRC is a heterogeneous disease. Tumors differ widely in clinical presentation, molecular features and prognosis. Treatment that works for one patient may not be effective for another due to such differences. Cancer cells are also adaptable and may have, or develop, a variety of resistance mechanisms.

Treatment is further complicated by how the patient’s immune system and other cells in the tumor microenvironment respond to the presence of the tumor and to CRC treatment. Changes in diet and physical activity can also affect response to treatment. Identifying biomarkers that can predict metastasis and drug effectiveness, and which can be routinely used in the clinic, are important in order to provide optimal treatment efficiently.

Developing personalized treatment strategies in CRC and identifying biomarkers that predict individual drug response are also vital in order to quickly provide optimal treatment for the individual CRC patient and reduce the risk of side-effects and delay.

This theme focuses on optimizing and tailoring CRC treatment by identifying novel biomarkers that can predict cancer progression, assessing individual drug responses, and identifying signaling pathways that drive cancer progression and metastasis. The theme also addresses the role of nutrition and the patient’s immune system in CRC progression, and how these can be targeted to optimize and tailor the effect of CRC drug treatment.

Aims

1. Determine if expression of small RNAs and circulating tumor DNA can predict cancer progression and response to treatment
2. Identify and target gene expression and signaling pathways that drive metastasis
3. Predict the effect of different anti-cancer drugs in individual cancer patients by applying computer simulations to analyze drug responses in patient-derived samples in vitro
4. Identify drug-drug interactions and how these affect the individual patient’s response using computer models calibrated to each patient’s cancer
5. Identify epigenetic modifiers that can be targeted in CRC treatment
6. Determine how immune cells and inflammatory signals in the tumor microenvironment affect cancer progression and how these can be targeted in CRC treatment
7. Determine the effect of nutrition in cancer progression and identify specific biomarkers (single nucleotide variants) that predict if a given CRC patient will benefit from dietary poly-unsaturated fatty acids treatment
8. Develop novel imaging protocols for early assessment of chemotherapy response in CRC patients
9. Identify metabolic and proteomic biomarkers in CRC for improved risk stratification and assessment of response to therapy
10. Investigate how tumour diversity is generated and its impact on treatment response and clinical outcomes

Contact

Eva Hofsli, Associate Professor

Theme leader: Arne Wibe

An increasing number of CRC patients are surviving their cancer, but many of these individuals have to deal with a variety of debilitating long-term effects.

The long-term effects can be fatigue, pain, neuropathy, bowel dysfunction, incontinence and sexual dysfunction. Distress, anxiety and depression are also common side-effects.

The choice of treatment, as well as diet and physical activity can affect the long-term outcome of CRC and improve the quality of life of CRC patients.

The effect of physical activity and specific nutrition during radiotherapy is being studied in randomized trials on patient cohorts. Clinical studies are being done to develop new technologies for colorectal cancer surgery aiming to reduce the surgical trauma for patients with less advanced disease, thereby reducing the chances of complications and long-term side effects. Different medical, radiological and nutritional treatments are also being evaluated in animal models to determine which combinations improve the long-term outcome of CRC.

Aims

1. Investigate the effect of a minor vs. a major surgical procedure on local recurrence and survival for early rectal cancer
2. Determine the effect of plyometric exercise on bone and muscle deterioration during radiotherapy
3. Determine the effect of physical exercise and nutrition on fatigue, body composition and metabolic syndrome in colon cancer patients receiving adjuvant chemotherapy treatment in a randomized multicenter study
4. Conduct a randomized trial to investigate how physical exercise affects incontinence, sexual function, osteoporosis and sarcopenia in rectal cancer patients undergoing preoperative radiochemotherapy

Contact

Mara Martin Alonso, Group leader