| Non-Small Cell Lung Cancer and Hsp90
Disease background and scientific rationale
The American Cancer Society (ACS) reports that lung cancer is the leading cause of cancer death for both men and women. The ACS estimates that approximately 214,000 new cases of lung cancer will be diagnosed in the United States in 2007. Non-small cell lung cancer (NSCLC) is the most common form of lung cancer, accounting for about 85% of all lung cancers.
In some cases of NSCLC, specific mutations have been identified in a cellular signaling enzyme called epidermal growth factor receptor (EGFR). Patients with NSCLC with mutations in EGFR have been found to benefit from existing therapies that block EGFR signaling, including targeted kinase inhibitors. Unfortunately, additional resistance mutations in EGFR often lead to disease progression even in patients who initially respond to kinase inhibitor therapy, necessitating the development of new therapeutics with novel mechanisms of action.
Multiple cellular proteins or pathways have been linked to the progression and resistance to therapy of non-small cell lung cancer, including mutated EGFR, Akt, and cMet. These proteins are all client proteins of Hsp90 and in preclinical experiments are degraded in cancer cells upon treatment with
retaspimycin, also known as IPI-504, leading to cancer cell death. This suggests that Hsp90 inhibition with retaspimycin is a promising area for clinical investigation in NSCLC. Furthermore, with a complementary, novel mechanism of action, inhibition of Hsp90 has the potential to aid in overcoming resistance to kinase inhibitor therapy.
Clinical trials
Preliminary data from the Phase 1 portion of Infinity’s open-label Phase 1/2 clinical trial of retaspimycin hydrochloride in patients with advanced metastatic NSCLC were presented at the AACR-NCI-EORTC International Conference in October 2007. Preliminary evidence of biological activity was reported in a heavily pretreated population of patients. In seven of nine evaluable patients, disease stabilization by RECIST (Response Evaluation Criteria in Solid Tumors) was achieved over at least one cycle of administration. One patient with a mutation in EGFR and prior history of progression on targeted kinase inhibitors experienced Stable Disease for more than 6 months. In addition, four of four evaluated patients who underwent positron emission tomography (PET) imaging revealed a decrease in tumor metabolic activity in response to retaspimycin hydrochloride administration as measured by uptake of
18-fluorodeoxyglucose, an imaging agent.
- Click here for more information on Infinity’s ongoing clinical trial in NSCLC.
To help you learn more about NSCLC, we have provided links to the following lung cancer support groups:
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