AstraZeneca and Lilly to Collaborate on Immuno-Oncology Combination Clinical Trial in Solid Tumours

“AstraZeneca and Eli Lilly and Company (Lilly) today announced that they have entered into a clinical trial collaboration to evaluate the safety and preliminary efficacy of AstraZeneca’s investigational anti-PD-L1 immune checkpoint inhibitor, MEDI4736, in combination with ramucirumab (CYRAMZA®), Lilly’s VEGF Receptor 2 antiangiogenic cancer medicine. The planned study will assess the combination as a treatment for patients with advanced solid tumours.

“The Phase I study is expected to establish the safety and a recommended dosing regimen, with the potential to open expansion cohorts in various tumours of interest, for the combination of MEDI4736 and ramucirumab. Under the terms of the agreement, the trial will be sponsored by Lilly. Additional details of the collaboration, including tumour types to be studied and financial terms, were not disclosed.”

ASCO 2014 Lung Cancer Roundup

Every year, thousands of people gather in Chicago, Illinois, for the American Society of Clinical Oncology (ASCO) Annual Meeting. The largest meeting of its kind, ASCO brings together doctors, researchers, nurses, patient advocates, pharmaceutical company representatives, and more to discuss the latest in cancer research. Here are some of the most exciting new developments in lung cancer research presented last week at ASCO 2014: Continue reading…

Cabozantinib Inhibits Prostate Cancer Growth and Prevents Tumor-Induced Bone Lesions

“Purpose: Cabozantinib, an orally available multi-tyrosine kinase inhibitor with activity against MET and vascular endothelial growth factor receptor 2 (VEGFR2), induces resolution of bone scan lesions in men with castration-resistant prostate cancer bone metastases. The purpose of this study was to determine whether cabozantinib elicited a direct anti-tumor effect, an indirect effect through modulating bone, or both. Experimental Design: Using human prostate cancer xenograft studies in mice we determined cabozantinib’s impact on tumor growth in soft tissue and bone. In vitro studies with cabozantinib were performed using (1) prostate cancer cell lines to evaluate its impact on cell growth, invasive ability and MET and (2) osteoblast cell lines to evaluate its impact on viability and differentiation and VEGFR2. Results: Cabozantinib inhibited progression of multiple prostate cancer cell lines (Ace-1,C4-2B, and LuCaP 35) in bone metastatic and soft tissue murine models of prostate cancer, except for PC-3 prostate cancer cells in which it inhibited only subcutaneous growth. Cabozantinib directly inhibited prostate cancer cell viability and induced apoptosis in vitro and in vivo and inhibited cell invasion in vitro. Cabozantinib had a dose-dependent biphasic effect on osteoblast activity and inhibitory effect on osteoclast production in vitro, that was reflected in vivo. It blocked MET and VEGFR2 phosphorylation in prostate cancer cells and osteoblast-like cells, respectively. Conclusion: These data indicate that cabozantinib has direct anti-tumor activity; and that its ability to modulate osteoblast activity may contribute to its anti-tumor efficacy.”

Scientists Refine and Develop New Strategies to Target Bone Metastases

Metastasis is responsible for most cancer deaths, but the organs to which specific types of cancers migrate differ. Prostate cancers tend to metastasize to bone tissue, causing bone-related complications. The symptoms of bone metastases can be very painful and disruptive. Fortunately, some patients can benefit from therapies developed specifically to treat these complications. Continue reading…

A Dose-Ranging Study of Cabozantinib in Men with Castration-Resistant Prostate Cancer and Bone Metastases

“Cabozantinib is an oral MET/VEGFR2 inhibitor. A recent phase II study of cabozantinib (100 mg daily) showed improved bone scans in subjects with metastatic castration-resistant prostate cancer (mCRPC), but adverse events (AE) caused frequent dose reductions. This study was designed to determine the efficacy and tolerability of cabozantinib at lower starting doses…”

Tumor VEGF:VEGFR2 autocrine feed-forward loop triggers angiogenesis in lung cancer

The molecular mechanisms that control the balance between antiangiogenic and proangiogenic factors and initiate the angiogenic switch in tumors remain poorly defined. By combining chemical genetics with multimodal imaging, we have identified an autocrine feed-forward loop in tumor cells in which tumor-derived VEGF stimulates VEGF production via VEGFR2-dependent activation of mTOR, substantially amplifying the initial proangiogenic signal.