Therapeutic Modalities of Lung Cancer06/02/17
Lung cancer remains a leading cause of cancer-related deaths worldwide. Surgical resection is the best therapeutic option for patients with non-small cell lung cancer (NSCLC). However, survival rates are directly affected by incomplete removal of the primary tumor and other malignant sites that cannot be identified. On Target Laboratories (OTL) is developing tumor targeted- fluorescent dye that will visualize and enable image-guided resection of NSCLC, representing a significant advancement over current surgical limitations in pulmonary resection.
Lung cancer is the major cause of cancer-related death worldwide, amounting to over 1.4 million fatalities per year. The cumulative cost of treating lung cancer patients has been estimated at $20bn (~€18.7bn) per year in the US. The major causes of lung cancer are smoking (85%), genetic factors (8%), exposure to radon gas, asbestos, polluted air, and second-hand smoking. Based on the size and immunohistochemical analysis, lung cancer can be categorised into two major types as NSCLC and small-cell lung carcinoma (SCLC). NSCLC can be further divided into subtypes such as adenocarcinoma, squamous-cell carcinoma and large-cell carcinoma.
Diagnosis of lung cancer is accomplished by chest X-ray (AKA chest radiography) and computed tomography (CT) scans followed by biopsy. Treatment of NSCLC commonly involves surgery, chemotherapy, and/or radiotherapy, whereas treatment of SCLC limited to chemotherapy and radiotherapy. Surgery is an important therapeutic modality in patients with NSCLC and the percentage of patients undergoing surgery with therapeutic intent varies with the stage of the cancer. In early stage (1 and 2) NSCLC, over 70% of patients undergo surgery. In 53% of such patients, this may be the only therapeutic modality required without the need for chemotherapy and/or radiation therapy. Hence, for optimal surgical resection of the cancer, it is important for the surgeon to locate. Given that surgery may be the primary therapeutic modality in a substantial proportion of patients with lung cancer, it is important that all cancerous tissue be excised. Given the compromised baseline pulmonary status of these patients (as the majority of them are smokers), it may also be important that as much as possible of non-cancerous lung tissue be left intact. Moreover, the lymph node status of the patients is important in determination of therapeutic options. Metastasis to the mediastinal lymph nodes would be an indicator of not proceeding with excisional therapeutic surgery. Sometimes this is only detected once the thoracic cavity is open, and the process can delay the needed chemotherapy.
Additionally, involvement of the lymph nodes determines adjuvant therapy. Lymph nodes that harbour metastatic cancer cells often feel and look normal, and may not have been detected by pre-operative imaging techniques like X-ray or CT scans. Pre-operative imaging techniques also have the limitation of not providing real-time information during surgery as they are confined to static images. Intra-operative pathological procedures such as frozen section are time consuming and miss tumour cells often. Clearly, new innovative technologies that help to remove the complete tumour with negative margins, identify micro-metastases, including lymph nodes harbouring metastatic cancer cells, and leave non-cancerous lung tissues intact are needed.
Image-guided surgery is an emerging technique that helps surgeons to more accurately identify malignant tissues and remove them without compromising healthy tissues. One of the inherent challenges in the field is the development of imaging agents that are specific and sensitive for the cancer tissue, particularly occult lesions that would not have been identified by usual techniques. Non-targeted near infrared (NIR)-dyes such as indocyanine green (ICG) have been used in image-guided surgeries for cancer; however, ICG has been found to have significant limitations with respect to sensitivity and specificity in the identification of tumour tissue. OTL is developing NIR agents that selectively label NSCLC tissues using receptors that are overexpressed on the NSCLC cells, and a phase II clinical trial in NSCLC patients will start in the autumn of 2017. Real-time visualisation not only of the complete tumour margins but also potentially other malignant sites outside the primary tumour area will enable complete surgical removal of primary and other tumour tissues. Moreover, fluorescence imaging could aid in the surgical decision to conserve lung function by removing only the diseased tumour tissue rather than lobectomy or pneumonectomy.
About the author
Sumith A Kularatne, Ph.D., is the vice-president of research and development at OTL. He has pioneer experience in drug designing on both small molecule ligands- and antibody-targeted drugs under the guidance of Philip S Low at Purdue University, West Lafayette, Indiana, USA, and Peter G Schultz at The Scripps Research Institute, San Diego, California, USA.
Kularatne’s scientific efforts have resulted in six drug candidates in human clinical trials with three different companies, over 50 US and foreign issued/pending patents, and over 30 peer-reviewed publications. He has given multiple invited seminars/lectures in prestigious conferences as well as in multiple institutes and has received several international and national awards.
Sumith A Kularatne, PhD
Vice-President of Research & Development
On Target Laboratories, LLC
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