Alexander Leandros Lazarides, MD, resident at Duke University Medical Center, discusses research regarding margin assessment in patients with sarcoma.

Negative surgical margins are associated with lower local recurrence and improved overall survival, explains Lazarides. However, it is only after surgery that the pathologist can evaluate a tumor sample to determine whether a negative margin was achieved or not. Results can take up to 2 weeks to return, at which point any residual disease that may have been left behind may have spread.

At Duke, investigators have developed an activatable fluorescent probe that has the potential to assess margins intraoperatively. The fluorescent probe is activated by cathepsin proteases, which are overexpressed in sarcoma, explains Lazarides. Once the primary tumor is taken out, surgeons can insert the probe to detect residual disease. This research has led to the development of a laser ablation system, which has been tested in mice as a way of killing remaining malignant cells, concludes Lazarides. 

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Alexander Leandros Lazarides, MD, discusses research regarding margin assessment in patients with sarcoma.

Dr. Lazarides on Research Regarding Margin Assessment in Sarcoma

Alexander Leandros Lazarides, MD, resident at Duke University Medical Center, discusses CRM1 as a potential target in osteosarcoma.

In an in vitro cell line analysis of osteosarcoma, CRM1 inhibitors were found to be effective in killing cancer cells, says Lazarides. CRM1 is expressed across several different cells and cancer cell types, and higher expression confers a worse prognosis.

CRM1 is an essential nuclear export factor which transports products from the nucleus into the cytoplasm of the cell so that they can be processed into more functional proteins. In an in vivo trial in mice, a CRM1 inhibitor had a high effect on limiting tumor growth compared with controls, further validating CRM1 as a target in osteosarcoma, concludes Lazarides.

Dr. Lazarides on CRM1 as a Potential Target in Osteosarcoma

Alexander Leandros Lazarides, MD, resident at Duke University Medical Center, discusses some of the current challenges in moving the field forward in osteosarcoma.

Since the use of chemotherapy in the 1970s, few advancements have been made in this field, says Lazarides.

Although osteosarcoma has a bimodal distribution, it disproportionally affects a pediatric population, explains Lazarides.

Additionally, the existing model for osteosarcoma may not be sufficient as the disease is highly heterogeneous, says Lazarides. As such, targeting a specific pathway has proven difficult. 

The identification of novel agents and developing a more efficient drug discovery model is critical to push the field forward, concludes Lazarides. 

Alexander Leandros Lazarides, MD, discusses some of the current challenges in moving the field forward in osteosarcoma.

Alexander Leandros Lazarides, MD

Articles

Dr. Lazarides on Research Regarding Margin Assessment in Sarcoma

Dr. Lazarides on CRM1 as a Potential Target in Osteosarcoma

Dr. Lazarides on Challenges in Moving the Field of Osteosarcoma Forward