- Sensitization and Rapid, Noninvasive Assessment of Lung Cancer Response to Therapy
- Innovative Strategy for Treatment of Lung Cancer: Inhalatory Codelivery of Anticancer Drugs and siRNA for Suppression of Cellular Resistance
- A Novel Therapeutic Target for Squamous Cell Lung Cancer
Non-small cell lung cancer is generally treatable with surgery, radiation, and/or chemotherapy. Currently, the effectiveness of treatment cannot be accurately assessed until several months after its completion, introducing a significant delay regarding treatment decisions should the patient fail to respond. To address this challenge Dr. Arif Ali is working on developing a PET imaging modality that will indicate likely tumor response to a given treatment within the first few days of administration. Dr. Ali hypothesizes that the tumor expression of GRP78, a protein whose expression level has been associated with chemotherapy response, can be non-invasively measured and monitored to assess tumor response to chemotherapy or radiation. Dr. Ali is currently confirming whether GRP78 levels correlate with chemotherapy and radiation treatment in patient samples and developing a PET tracer conjugated with a peptide with specific affinity for GRP78. The correlation of PET-GRP78 tumor uptake with chemotherapy and radiation response will be assessed in animal models.
Innovative Strategy for Treatment of Lung Cancer: Inhalatory Codelivery of Anticancer Drugs and siRNA for Suppression of Cellular Resistance
Posted November 15, 2011
Dr. Oleh Taratula, Ph.D. and Dr. Tamara Minko, Ph.D. Rutgers University
Insufficient chemotherapeutic efficacy may be one of the main reasons for the poor prognosis in patients diagnosed with lung cancer, which takes more lives each year than all other major cancers combined. Systemic administration of chemotherapy can result in several severe adverse side-effects, and the dose is often limited to what the patient can tolerate rather than what is needed to kill the cancer. Moreover, tumors often rapidly develop drug resistance upon exposure via "pump" (i.e., active drug efflux from tumor cells) or "nonpump" (i.e., anti-apoptotic defense of tumor cells) mechanisms. Drs. Oleh Taratula and Tamara Minko have sought to overcome these issues by developing a novel inhalable drug delivery system composed of biocompatible nanoparticles conjugated with a tumor-targeting peptide, anti-cancer drugs (doxorubicin or cisplatin), and siRNAs as suppressors of cellular drug resistance. Testing in mice has demonstrated that nanoparticles impregnated with therapeutic agents show lung tumor-specific accumulation after inhalation along with limited systemic toxicity and adverse side effects to healthy organs. Based on these results, Investigators plan on conducting additional studies to further develop this system for lung cancer treatment.
While lung cancer continues to be the principal cause of cancer-related deaths in the United States, treatment of lung adenocarcinomas with inhibitors of the epidermal growth factor receptor tyrosine kinase or the anaplastic lymphoma kinase has led to remarkable responses in a subset of lung adenocarcinoma patients whose tumors harbor genetic alterations in either of these kinases. However, little progress has been made in the treatment of lung cancer patients with lung squamous cell carcinoma (SCC), the second most common type of lung cancer. Dr. Peter Hammerman, recipient of an FY09 LCRP Clinical Fellow Research Award, is currently identifying and characterizing novel therapeutic targets for SCC by utilizing a functional genomic approach. Dr. Hammerman has identified the discoidin domain receptor 2 (DDR2) kinase gene as a target of recurrent somatic mutations in squamous lung tumors; therefore, Dr. Hammerman is focusing his efforts on characterizing whether DDR2 is a therapeutic target for the treatment of SCCs. In his recent publication in Cancer Discovery, the flagship journal of the American Association of Cancer Research, he identified 11 novel mutations in DDR2 from 290 human SCC samples with a mutation frequency of 3.8%. In addition, he found that dasatinib, a drug currently used for leukemia, can inhibit the proliferation of DDR2-mutated SCC cell lines both in vitro and in vivo. This suggests that DDR2 may be the first therapeutic target in lung SCC with existing clinically approved drugs, thus leading the way for clinical trials testing the efficacy of tyrosine kinase inhibitors for lung SCCs. Dr. Hammerman plans to open a trial of dasatinib for squamous cell lung cancer patients later this year.