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Colorectal cancer (CRC) is the third most common cancer worldwide, and extensive research has been done on the early stages of this disease. Surprisingly, there has been very little focus on metastatic spread to other organs, such as the peritoneum, which in fact is the leading cause of death in these patients. By digging deep into the molecular facets of this advanced stage of colorectal cancer, we hope to gain insights that can help to improve survival of patients with peritoneal metastasis (PM).
Peritoneal metastasis occurs when cancer cells spread from the tumor in colon or rectum to the peritoneum, which is a thin membrane that supports and covers the organs of the abdominal cavity. This advanced stage of cancer is present in about 10 percent of patients at the time of diagnosis, and 25-35 percent upon colorectal cancer recurrence. Traditional chemotherapy has not been very effective, and the prognosis for these patients is extremely poor, with fatal outcome within a year. Fortunately, a new treatment combining surgery and heated chemotherapy has shown promising results, and a chance for long-term survival or even cure may now be offered to some of these patients. However, this treatment is very demanding with high risk of complications and variable outcome. Thus selecting the patients that will benefit from this treatment is crucial.
As the national treatment program for PM-CRC is located at the Norwegian Radium Hospital, we have a unique opportunity to study this disease, using tumor samples harvested from patients during surgery. In this project we aim to find molecular abnormalities that can help us to predict treatment response, determine disease progression, and increase our understanding of special features such as chemotherapy resistance. In addition we hope to find alterations in the tumor that can be exploited in novel cancer therapy. Basically, we will extract DNA, mRNA and protein from the tumor tissue and use advanced molecular technology, such as next generation sequencing, to map molecular aberrations. Bioinformatic tools, developed by combining computer science, mathematics and statistics, will be used to discover molecular patterns associated with clinical patient characteristics and treatment outcome. Interesting findings could be further explored in cell lines, animal models and clinical trials.
Hypoxia-induced alterations of G2 checkpoint regulators
Mol Oncol, 10 (5), 764-73
PLK1-inhibition can cause radiosensitization or radioresistance dependent on the treatment schedule
Radiother Oncol, 110 (2), 355-61
A genetic screen identifies BRCA2 and PALB2 as key regulators of G2 checkpoint maintenance
EMBO Rep, 12 (7), 705-12
The amount of DNA damage needed to activate the radiation-induced G2 checkpoint varies between single cells
Radiother Oncol, 101 (1), 24-7