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Centre for Cancer Biomarkers CCBIO

Anti-Angiogenic Treatment

Dr. Straume has a background in medical oncology with special interest in cutaneous melanoma, renal cancer, and breast cancer. Straume’s research group focuses on clinical cancer research.

Portrait photo.
Photo:
Ingvild Festervoll Melien Illustration: Gaute Hatlem/Eli Vidhammer

Research focus

The main research goal is to identify predictive biomarkers in clinical materials. The group studies populationbased patient series, clinical trial series as well as single cancer patients treated in the clinic.

Projects

  1. 1. Clinical trial: 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 advanced nonresectable (stage IIIc) or metastatic (stage IV) melanoma. The main objective is to analyze safety and efficacy of BGB324 in combination with MAPK inhibitors and immunotherapy as well as to identify predictive markers of response.

    2. Clinical trial: A national, multicenter, interventional study in patients with unresectable or metastatic melanoma (IPI4). The goal is to identify predictive value of VEGF related biomarkers.

    3. Clinical trial: Efficacy of bevacizumab monotherapy in treatment of metastatic melanoma and predictive value of angiogenic markers. The goal is to analyze predictive markers of response in liquid biopsies.

    4. Clinical trial: Predictive markers of response to sunitinib in treatment of metastatic renal cell carcinoma. The goal is to analyze predictive markers of response in liquid biopsies and tissue biopsies.

    5. Research project: Importance of physical trauma on time to recurrence after primary treatment of breast cancer, by analyzing patient series and blood samples from patients undergoing different types of breast surgery. 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.

    6. Research project: The role of epithelialto-mesenchymal transition (EMT) and cancer stem cell traits in breast cancer metastasis, by analyzing the role of the EMT associated AXL receptor in initiation and progression of breast cancer.

    7. Research project: Targeting cancer stem cells with AXL receptor inhibitors to improve the treatment of cancer, by using different preclinical models to study efficacy of the AXL inhibitor BGB324 in cancer. In particular, the combinations of BGB324 with immune check point inhibitors are encouraging.

Important results

Some selected results from the projects above:

1: Overall, 54 patients have received treatment in the trial as of Jan 2020, and five regional centers have recruited patients. In June 2019, an interim analysis showed that the treatment was safe, and inclusion continues.

3: In melanoma patients treated with bevacizumab, circulating tumor DNA (ctDNA) detected by digital droplet PCR was a useful biomarker for both monitoring and predicting response to bevacizumab.

4: The group has found that elevated baseline IL6 in plasma predicts poor response in renal cell carcinoma patients treated with sunitinib.

5: The group has quantified surgical complications occurring after breast reconstructions in breast cancer patients and results show a significant change in recurrence dynamics in patients who experience complications.

Current challenges in the field

First, the lack of reliable and robust predictive biomarkers of response to treatment for cancer is a major challenge. Second, in most cancer types, the response to immune checkpoint inhibitors is poor. We need to develop new strategies to increase response rates in these cancer types. Third, cancer is a systemic disease, and the majority of cancer deaths are due to metastatic disease. We need to increase our understanding on why micrometastatic foci of cancer cells escape from dormancy and cause overt metastatic disease.

Future plans

The group will continue collecting data and patient materials (blood/tissues) in clinical trials. A new phase 2 clinical trial in renal cell carcinoma combining cryoimmune therapy with immune checkpoint inhibitors will be initiated.

 

2016 Spring Interview

Oddbjørn Straume and his group are working on several promising projects, including research on melanoma, kidney cancer and breast cancer.

Can you tell us about your work and what drives you?

"Melanoma is my personal favorite among all cancers. The melanoma is a kind of prototype malignancy for many kinds of tumor processes, such as interactions with the immune system and the tumor microenvironment, cellular plasticity as well as angiogenesis. I also have research projects on treatment of metastatic kidney cancer. In addition, we study the relation between physiologic processes, such as wound healing, stress responses or tissue trauma, and breast cancer recurrence. In the clinic, I work with all these three cancer types."

How promising are the results so far?

"We set out to identify cancer biomarkers that could be used to guide good clinical decision making. This is a huge challenge, and I am respectful of how difficult it is to predict the behavior of a disease that by definition is unpredictable, due to tumor cell heterogeneity and complex interactions with the host tissues. Nevertheless, I think that the time spent on building up clinical series with complete follow-up and treatment response endpoints will be worthwhile. Several of the candidate biomarkers studied in the CCBIO groups need validation in these kinds of datasets before they can be introduced in the clinic. In particular, a planned randomized phase Ib/II clinical trial will be specifically designed to validate predictive biomarkers of anti-Axl targeted treatment."

What do you hope for the future regarding coming research?

"I hope that the time invested in our clinical trials so far will pay off by resulting in new promising predictive markers useful for the clinicians when planning individualized treatment. I also hope that our research will increase the understanding of tumor biological processes, and maybe, if we are lucky, lead to new targets for future treatment of cancer."

PubMed Publications