Identifying new druggable targets is desired to meet the needs for effective cancer treatments. To this end, we previously reported the efficacy of a therapeutic peptide called CT20p that displays selective cytotoxicity through inhibition of a multi-subunit, protein-folding complex called Chaperonin-Containing TCP-1 (CCT). To investigate the role of CCT in cancer progression, we examined protein levels of CCT subunits in liver, prostate, and lung cancer using human tissue microarrays. We found that these cancers expressed higher levels of CCT2 as compared to normal tissues. Small cell lung cancer (SCLC) stood out as having statistically significant difference in CCT2. Higher levels of CCT2 in tumors from lung cancer patients were also associated with decreased survival. Using SCLC cell lines, we observed detectable amounts of CCT subunits and cells were susceptible to killing by CT20p. Treatment with CT20p, delivered to cells using polymeric nanoparticles, was cytotoxic to all SCLC cell lines, decreasing the levels of CCT client proteins like STAT3. In contrast, treatment with a STAT3 inhibitor was effective in one of the SCLC cell lines. While we found that CCT levels could vary in cell lines, normal tissues had low levels of CCT and minimal toxicity to liver or kidney function was observed in mice treated with CT20p. These results indicate that in SCLC, changes in CCT levels could be used as a biomarker for diagnosis and that targeting CCT for inhibition with CT20p is a promising treatment approach for those cancers such as SCLC that currently lack targeted therapeutics.

No abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial pneumonia with a median survival of 3 years after diagnosis. Acute exacerbation of IPF (AE-IPF) is now identified as a life-threatening complication. It presents as worsening dyspnea with new ground glass opacities superimposed upon a radiographic usual interstitial pneumonia (UIP) pattern. It is a diagnosis of exclusion. The prognosis of AE-IPF is poor and treatment strategies lack standardization. In order to rule out any reversible etiology for an acute decompensation of a previously stable IPF patient diagnostic modalities include computerized tomographic angiogram (CTA) coupled with high-resolution computerized tomography (HRCT) imaging of the chest, bronchoalveolar lavage (BAL) and echocardiogram with bubble study. Avoiding risk factors, identifying underlying causes and supportive care are the mainstays of treatment. Anti-inflammatory and immunosuppressant medications have not shown to improve survival in AE-IPF. Most of the patients are managed in a critical care setting with mechanical ventilation. Lung transplantation is a promising option but most institutions are not equipped and not every patient is a candidate.

Where available, EBUS-TBNA of centrally located peribronchial lung lesions should be given a strong consideration given its high diagnostic yield.