Value Proposition:
· Combination treatment strategy enhances existing chemotherapy treatment regimens to improve long-term survival.
· Integration of small molecules with conventional chemotherapy regimens establishes new treatment options for drug-resistant and recurrent lung cancer.
· Cancer stem cells (CSCs) are a target in other cancers, such as bladder cancer, head and neck cancer, breast cancer and glioblastoma, expanding potential therapeutic applications of this combination therapy.
· Small molecules can be adapted as research tools to study CSC pathways in other cancers.
Technology Description:
Researchers at Johns Hopkins are developing a combination therapeutic strategy to target cancer stem cells (CSCs) in lung adenocarcinoma. They have identified genes in a CSC-specific pathway that contribute to their drug resistance and have further found small molecules that inhibit these genes. Studies have demonstrated efficacy of these small molecules in mice where combination of their small molecules with conventional chemotherapy suppressed the growth of human lung adenocarcinoma tumors.
Unmet Need:
Despite treatment advances, lung cancer is still the leading cause of cancer deaths in the United States, with late-stage diagnosis having a 5-year survival rate of only 12%. There were an estimated 236,760 new cases of lung cancer and 130,180 lung cancer deaths in the United States in 2022, according to the American Cancer Society. Among subtypes of lung cancer, lung adenocarcinoma is the most common in the United States. Treatment options include surgical resection, radiation, and chemotherapy; however, the presence of CSCs reduces treatment efficacy and increases the likelihood of relapse and/or metastasis. Following chemotherapy, CSCs may persist and reestablish tumors following remission. Patients with CSCs have poor prognosis following treatment by current methods. Therefore, there is a strong need for a CSC-targeted therapy that can enhance current treatments and improve long-term survival in lung adenocarcinoma.
Stage of Development:
· Preclinical studies have demonstrated significant tumor growth suppression with combination small molecule-chemotherapy in human lung and bladder tumors in xenograft mouse models.
· Currently evaluating the potential for combination with immunotherapy to improve outcomes in lung adenocarcinoma and urothelial carcinoma of bladder.
Data Availability:
· Data is available upon request.
Publication:
Shibata M…Hoque MO. Concurrent Targeting of Potential Cancer Stem Cells Regulating Pathways Sensitizes Lung Adenocarcinoma to Standard Chemotherapy. Mol Cancer Ther. Published October 19, 2020. doi: 10.1158/1535-7163.MCT-20-0024.
