Not very, according to the REACT Study conducted by the Imperial College London. The study was predicated on the importance of COX-2 in driving inflammation that contributes to tumorigenesis. The thinking was that administering celecoxib (Celebrex), a COX-2 inhibitor, could reduce breast cancer progression, as suggested in smaller observational trials. Continue reading
Category Archives: Invasion & Metastasis
MET – an ideal target for antibody drug conjugate therapy, plus nivolumab
MET is a gene that encodes a receptor tyrosine kinase that is activated upon binding with hepatocyte growth factor (HGF, or Scatter Factor). Specifically, MET is a Continue reading
CANTOS trial of canakinumab demonstrates that inflammation is a lung cancer promoter
Cells need to accumulate multiple mutations in order to induce the 10 hallmarks of cancer: Continue reading
Platelet conjugates effectively deliver checkpoint inhibitors to tumors
Platelets are the second most abundant cellular component of blood. The platelet membrane contains an abundance of receptors to facilitate interactions with subendothelial matrix , other blood cells, and other platelets. The central role of platelets is in hemostasis, however, they also contain copious amounts of cytokines that induce inflammation. Continue reading
Osteopontin – a prognostic marker for cancer progression
Osteopontin (OPN) is a matrix protein that is expressed by osteoclasts, osteoblasts, dendritic cells, fibroblasts, hepatocytes, smooth and skeletal muscle cells, endothelial cells, and kidney cells. It interacts with many cell surface receptors including integrins and CD44. One of the major physiologic functions of OPN is the control of bone mineralization – by binding to specific apatitie crystal faces, it inhibits mineralization. But, OPN is also a pro-inflammatory cytokine that acts in many tissues to recruit monocytes and macrophages and induce cytokine secretion from leukocytes. As such, it has a critical role in tissue remodeling, inflammation, and tumorigenesis. Continue reading
Molecular switch of L-plastin plays role in cancer metastasis
Researchers from the University of Calgary reported that disruption of a region of L-plastin (LPL), a calcium binding protein, prevented cancer cells from invading. The area on LPL is called a “molecular switch.” On the basis of this work, the molecular switch has emerged as a new target for cancer treatment. Continue reading
Melanoma Metastases Enabled by Melanosomes
Researchers have identified vesicles containing micro-RNA are important in the aggressive biologic behavior of melanoma, a cancer that kills via metastasizing to distant sites from primary tumors that are quite small. Continue reading
Bristol Myers Acquire Cormorant for Anti-IL-8 Cancer Drug
BMS (Bristol Myers Squibb) acquired all of the outstanding capital stock of Cormorant, the private, Stockholm-based biotech company developing HuMax-IL8, for $520MM. HuMax-IL8, which is currently in Phase I/II trials, is a monoclonal antibody that targets interleukin-8 (IL-8), a protein is expressed by many solid tumors. IL-8 also suppresses the immune system and increases the ability of tumors to metastasize. Continue reading
Diffuse Gastric Cancer is Associated with Elevated GDF15 – Kristen D. De Wilde, Contributor
About 90% of stomach tumors are adenocarcinomas, which are subdivided into two main histologic types: (1) well-differentiated or intestinal type (IGC), and (2) undifferentiated or diffuse type (DGC). The intestinal type is related to corpus-dominant gastritis with gastric atrophy and intestinal metaplasia, whereas the diffuse type usually originates in pangastritis without atrophy. Diffuse gastric cancer (DGC) differs from the more common intestinal (IGC) type in that the former is less differentiated, has a poorer prognosis, and occurs more frequently in younger patients. Continue reading
Additional Drivers and Pathways in Basal Cell Carcinoma
The Sonic hedgehog (Hh) pathway is known to be important in basal cell carcinoma (BCC), which as an extremely common skin cancer that only rarely invades and metastasizes. An approved drug for patients with advanced BCC, Vismodegib (Erivedge), interferes with the Hedgehog pathway. The Patched (12 membrane-spanning receptor protein) normally disables Smoothened (7 membrane-spanning protein) rendering it functionally inert. This maintains transcription factor Gli in a cleaved state, acting as a transcriptional repressor. When Hedgehog proteins bind to Patched, Smoothened is released and protects Gli from cleavage. Uncleaved Gli travels to the nucleus and is an inducer of transcription, increasing Cyclin D1 and stimulating the cell cycle (proliferation). Vismodegib blocks the actions of Smoothened. It is administered orally in 150 mg capsules.