Oddbjørn Straume

Oddbjørn Straume completed his MD in Bergen in June 1996, and his PhD was completed in 2002. After 2002, he worked as an oncologist and researcher at Haukeland University Hospital (HUH), Department of Oncology, combined with a postdoc at the UiB, Department of Pathology. His UiB position is now professor, PI at CCBIO since CCBIO’s initiation, and he is currently head of the Department of Oncology at HUH. Straume has extensive clinical experience, comprehensive research expertise, and a broad professional network. He has been the coordinating investigator in 4 investigator-initiated clinical trials, including 1 RCT. In addition, he is the PI of more than 12 industry clinical trials.

Brief group presentation and history

The research group was established in 2013 as a CCBIO group. Oddbjørn Straume started his research career in Lars A. Akslen’s group as a medical student focusing on biomarkers in melanoma. Later, the focus was expanded to include new tumor biological processes, such as tumor immune responses and tumor dormancy. Later, as a clinical oncologist, these research areas were incorporated in clinical research and clinical trials.

Research focus

The main research goal is to identify predictive biomarkers in clinical materials. The biomarkers under investigation are all related to tumor biological processes and new treatment modalities for cancer patients, such as angiogenesis, tumor immune responses, tumor cell plasticity, epithelial to mesenchymal transition (EMT), and mechanisms associated with the escape from tumor dormancy (i.e. late relapses).

Subprojects

1. Clinical trial I. A phase Ib/II randomized open-label study of BGB324 in combination with pembrolizumab or dabrafenib/trametinib compared to pembrolizumab or dabrafenib/trametinib alone, in patients with melanoma. Axl has been linked with both a reduced response to PD-1 blockade and therapy resistance to BRAF-directed therapies in melanoma. Bemcentinib is a first-in-class, orally bioavailable, highly selective Axl inhibitor. BGBIL006 (NCT02872259) was designed to explore whether combinations with bemcentinib are safe and improve overall response rate (ORR) and duration of response. Patients were enrolled between 2017 and 2022. A daily dose of 200 mg Bem was well tolerated in combination with Pem or D/T. The most frequent Bem-related adverse effects were rash, diarrhea, fatigue, and increased transaminases. Significant differences in ORR, PFS or OS were not observed between standard treatments and the combinations with Bem. In analyses of baseline biomarkers, the group did not identify subgroups of patients with increased response to combinations with Bem. The following biomarkers predicted improved response to Pem; high CD8+ count high FOXP3 count, high PD-L1 in TIL, high AXL expression in inflammatory cells.

2. Clinical trial II. A national, multicenter, interventional study of ipilimumab in patients with unresectable or metastatic melanoma (IPI4). Ipilimumab was the first immune checkpoint inhibitor to show overall survival efficacy in melanoma. The drug is expensive and is associated with severe adverse effects. Thus, predictive markers for response are needed. The aim of this project is to identify predictive markers of response to ipilimumab in metastatic melanoma. The IPI-4 prospective trial represents the longest reported follow-up of a real-world melanoma population treated with ipilimumab and was recently published. The group has now collected tissue samples from primary tumors and pre-treatment metastatic biopsies and started analyzing the material for predictive markers.

3. Clinical trial III. Efficacy of bevacizumab monotherapy in the treatment of metastatic melanoma and predictive value of angiogenic markers. Anti-angiogenic treatments, such as bevacizumab, are widely in use. Still, predictive markers of response are lacking. The aim of this project is to identify predictive markers of response to bevacizumab in metastatic melanoma. This clinical trial has produced several papers describing predictive markers of response. So far, no markers have been regarded as strong enough to move forward to validation. β2-adrenergic signaling is a stress response mechanism that impacts numerous hallmarks of cancer. To the best of our knowledge, the Straume group is the first to show the correlation between strong expression of β2-adrenergic receptor and clinical benefit from bevacizumab.

4. Tumor dormancy project. Importance of physical trauma on time to recurrence after primary treatment of breast cancer. There is evidence to suggest that late recurrences in some tumor types, such as breast cancer, are synchronized and accelerated by systemic signaling in the body. The project is based on the hypothesis that dormant micrometastases can initiate tumor growth following a systemic burst of growth factors after surgery or trauma. By analyzing patient series as well as blood samples from patients undergoing different types of breast surgery or experiencing complications after surgery, the group aims to identify the relationship between systemic growth factor signaling and activation of dormant micrometastases. The group has published results confirming a significant correlation between time of surgery, extent of surgery, and changes in the recurrence dynamics in breast cancer patients. They have further quantified surgical complications occurring after breast reconstructions in breast cancer patients and show a significant change in recurrence dynamics in patients who experience complications.

Translational, clinical, and societal importance

The finding of a negative prognostic role of complications following surgery might be of significant clinical importance, and it adds to the hypothesis that systemic signaling after tissue insult might influence pre-existing dormant occult metastases. The cost-effectiveness analysis of the group’s proposed candidates of predictive biomarkers may become part of the total package of validation analyses that we do when assessing the value of new biomarkers, and thus has a societal impact.

Future perspectives from 2024

The group is currently establishing infrastructure and group competence to perform state-of-the art methodologies and computational approaches to maximize the impact of biopsy samples obtained from patients participating in clinical trials and to define a new precision medicine approach to improve immunotherapy efficacy for melanoma patients. In addition, they are planning new projects focusing on adaptive mutability as a universal stress response caused by cancer treatment, driving tumor cell heterogeneity and resistance.