A Novel Anti-CD20 PET Tracer for Non-Hodgkins Lymphoma
The CD20 antigen is an effective target in >90% of B-cell lymphomas. To achieve more rapid, higher contrast imaging of B-cells, compared to the full antibody, Natarajan and colleagues developed a novel 10 kDa anti-CD20 fibronectin (FN3) binder to monitor therapy. 64Cu-FN3CD20 was evaluated in a humanized CD20 transgenic mouse model for PET imaging. This PET tracer shows high specificity and exhibited a target tissue-to-blood ratio of 13-fold at 4 h. At 4h, 64Cu-FN3CD20 shows ten-fold greater signal-to-background than the 64Cu-rituximab antibody radiotracer. Thus, 64Cu-FN3CD20 tracer shows significant clinical promise for imaging early after tracer injection of lymphoma patients.
HAb18G/CD147, CD44s, STAT3 and Pancreatic Cancer
The failure of conventional chemotherapeutic agents on survival of patients with pancreatic cancer highlights an urgent need for novel treatment strategies. STAT3 plays a critical role in pancreatic cancer initiation and progression and represents a novel therapeutic target. However, STAT3 occupies a point of convergence for many signaling pathways; blockade of existed upstream signaling to STAT3 activation are not sufficient to abrogate STAT3 activation. This study identified HAb18G/CD147 as a novel upstream activator in STAT3-mediated pancreatic tumor development by forming signaling complex with CD44s. Furthermore, we showed that pancreatic cancer patients with high co-expression of HAb18G/CD147-CD44s-STAT3 had poor prognosis. This information is valuable for a better understanding of the relationship between inflammation and pancreatic cancer initiation and progression induced by STAT3. Our results also suggest HAb18G/CD147 as a novel therapeutic target for highly aggressive pancreatic cancer and as a surrogate marker in clinical trials of molecular therapy targeting STAT3.
Chemoradiation Plus Sorafenib for Soft-Tissue Sarcomas
PDGFR, VEGF, and VEGF-R are overexpressed in soft tissue sarcomas and VEGF-R targeted therapies have shown activity in advanced disease. To explore the role of an antiangiogenic agent combined with chemoradiotherapy in patients with high-risk extremity soft tissue sarcomas, Meyer and colleagues designed a phase I trial of sorafenib in combination with epirubicin, ifosfamide, and hypofractionated radiation. The maximum tolerated dose of sorafenib was 400 mg daily. Dynamic contrast-enhanced MRI was investigated as an imaging modality to assess early response to therapy, which showed a correlation between the biomarker ΔKtrans and histologic necrosis at the time of surgery.
Biomarkers Demonstrating Akt Inhibition
The translation of preclinically validated biomarkers to the clinical setting to assess the activity of targeted therapy is of crucial importance for drug development. Yan and colleagues examined the impact of the catalytic Akt inhibitor GDC-0068 on preclinical models and derived a ten-biomarker set of Akt inhibition. The behavior of these biomarkers was tested in pre- and on-treatment tumor biopsies from patients treated with GDC-0068 and confirmed that GDC-0068 is biologically active at clinically achievable concentrations. The application of this approach may be useful for the clinical development of other targeted compounds.
- ©2013 American Association for Cancer Research.