Illuminating Cancer Cells To Help Guide Surgery
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Surgery is used to treat many different types of cancer. Surgery, when used as a cancer treatment, is a procedure in which a surgeon identifies and removes the cancerous tissue from a patient’s body. To ensure the cancer doesn’t return it is critical that the surgeon is able to remove all of the cancer.
We recently spoke with Christopher Barys, Chief Executive Officer at On Target Laboratories to learn more about the novel cancer imaging agents they are currently developing and to discover how they can be used to help surgeons identify and resect cancerous lesions.
Laura Lansdowne (LL): For our readers that may not be as familiar with On Target Laboratories, could you tell us more about the company’s focus and primary goal?
Christopher Barys (CB): Ovarian cancer is the most lethal gynecologic cancer. Fifty three percent of women with ovarian cancer will not survive five years post diagnosis.1 However, overall survival for these patients increases from 36 to 86 months when all residual disease is resected during surgery.2,3
The story is similar for lung cancer. Lung cancer is the leading cause of cancer-related death in the United States (US).4 Shockingly, 30–55% of patients who receive surgery for non-small cell lung cancer will develop recurrence and ultimately die of their disease despite their surgical treatment.5,6
On Target Laboratories specializes in discovering and developing novel, imaging agents which bind to and illuminate cancer. This technology has particular relevance in cancer surgery by potentially improving a surgeon’s ability to identify additional cancerous lesions which may be difficult-to-find during the actual operation.
Move the "slider" across the image to reveal the illuminated cancerous tissue...
LL: How does On Target’s technology work?
CB: On Target’s technology is a guided imaging agent that combines a binding ligand and a fluorescent dye. The binding ligand is specific to receptors which are overexpressed on the membrane of a targeted cancer cell. When the molecule comes in contact with the targeted cells, it binds to the surface and is taken into the cell through the membrane wall. The cell will then fluoresce during surgery under infrared light.
In real-world clinical experience, patients receive an infusion of the imaging agent as part of their normal pre-operative preparation for the procedure. During surgery the surgeon turns on a near infrared camera to illuminate the cancerous tissue, displaying the precise location of the lesion on a screen directly adjacent to the patient. The surgeon is then able to plan their resection according to the location and extent of the cancerous tissue.
This technology may not only help localize the primary lesion but could help surgeons evaluate positive resection margins and identify cancerous lesions not seen on the pre-operative scans, potentially increasing the likelihood the patient emerges from the procedure without residual cancerous tissue.
LL: Could you highlight some of the novel compounds being developed at OTL?
CB: Ovarian, lung, prostate, and colorectal cancers account for the majority of in-patient cancer surgeries in the US.7 These diseases are On Target’s primary areas of focus.
To make the most significant impact for patients, On Target is focusing its discovery and development efforts on these cancer types, which are routinely treated with surgery and have considerable remaining patient unmet needs. We hope to improve surgical outcomes and reduce complications for these procedures by increasing the likelihood that the surgeon is able to completely remove the cancerous tissue.
On Target’s clinical stage portfolio consists of two imaging agents. OTL38 is the lead compound in the portfolio and is currently being studied in ovarian cancer and lung cancer. OTL78 is the second compound in development and is in clinical trials with a specific focus in prostate cancer.
In ovarian cancer, results from a Phase II clinical study showed that OTL38 enabled surgeons to detect at least one additional lesion not detected under white light in 48% of patients.8 A Phase III clinical study is currently being conducted to further evaluate the efficacy of OTL38 in ovarian cancer. Further, a Phase II clinical study recently completed to evaluate the safety and efficacy of OTL38 in lung cancer; final results are pending.
Illuminating Lung Cancer With OTL38. Credit: On Target Laboratories
LL: What impact could this technology have, both in terms of the surgeon operating, and the patient?
CB: Surgeons use X-rays, magnetic resonance imaging, computed tomography, positron emission tomography and/or ultrasound to determine the size and location of tumors before surgery. However, these imaging modalities have limitations in their ability to differentiate healthy and diseased tissue, often expose patients to radiation, and are rarely, if ever, used intra-operatively.
Currently, once a surgeon initiates the operation, he/she must rely on only their visual and tactile senses to adequately detect and remove the cancer. On Target’s technology has the potential to enable surgeons to see highlighted cancerous lesions, which may not be visible to the naked eye or located through touch.
We hope this technology will be an additional tool available to surgeons to support better outcomes for cancer patients. By providing surgeons with this information in real-time, at the moment of the procedure, this technology may enable improvements to patient intra-operative care, overall patient outcomes and reduce the cost to our healthcare system by eliminating additional unnecessary procedures.
Christopher Barys was speaking with Laura Elizabeth Lansdowne, Science Writer for Technology Networks.
References
1. Aletti, G., Dowdy, S., Gostout, B., Jones, M., Stanhope, C., & Wilson, T. et al. (2006). Aggressive Surgical Effort and Improved Survival in Advanced-Stage Ovarian Cancer. Obstetrics & Gynecology, 107(1), 77-85. DOI: 10.1097/01.aog.0000192407.04428.bb
2. Aletti, G., Dowdy, S., Gostout, B., Jones, M., Stanhope, C., & Wilson, T. et al. (2006). Aggressive Surgical Effort and Improved Survival in Advanced-Stage Ovarian Cancer. Obstetrics & Gynecology, 107(1), 77-85. DOI: 10.1097/01.aog.0000192407.04428.bb
3. Chang, S., Bristow, R., & Ryu, H. (2012). Impact of Complete Cytoreduction Leaving No Gross Residual Disease Associated with Radical Cytoreductive Surgical Procedures on Survival in Advanced Ovarian Cancer. Annals of Surgical Oncology, 19(13), 4059-4067. DOI: 10.1245/s10434-012-2446-8.
4. Lung Cancer Fact Sheet. (2019). Retrieved 9 October 2019, from: https://www.lung.org/lung-health-and-diseases/lung-disease-lookup/lung-cancer/resource-library/lung-cancer-fact-sheet.html
5. Sugimura, H., Nichols, F., Yang, P., Allen, M., Cassivi, S., & Deschamps, C. et al. (2007). Survival After Recurrent Nonsmall-Cell Lung Cancer After Complete Pulmonary Resection. The Annals of Thoracic Surgery, 83(2), 409-418. DOI: 10.1016/j.athoracsur.2006.08.046
6. Uramoto H, Tanaka F. (2014). Recurrence after surgery in patients with NSCLC. Transl Lung Cancer Res. 3(4):242-249. DOI: 10.3978/j.issn.2218-6751.2013.12.05.
7. Orosco, R., Tapia, V., Califano, J., Clary, B., Cohen, E., & Kane, C. et al. (2018). Positive Surgical Margins in the 10 Most Common Solid Cancers. Scientific Reports, 8(1). DOI: 10.1038/s41598-018-23403-5
8. Randall, L., Wenham, R., Low, P., Dowdy, S., & Tanyi, J. (2019). A phase II, multicenter, open-label trial of OTL38 injection for the intra-operative imaging of folate receptor-alpha positive ovarian cancer. Gynecologic Oncology, 155(1), 63-68. DOI: 10.1016/j.ygyno.2019.07.010
