We have written previously about the Warburg Effect, the observation that cancer cells “bypass normal cellular respiration, that is, glucose converted to pyruvate through glycolysis, and the sequential oxidation of pyruvate through the Krebs Cycle in the mitochondria. Instead, tumor cells divert pyruvate to lactate dehydrogenase (LDH), which reduces pyruvate into lactate.” Continue reading
Category Archives: Tumor Microenvironment
CARMA – Chimeric Antigen Receptor Macrophages
CARMA Therapeutics, a company that develops chimeric antigen receptor technology, not for T-cells (CAR-T cells), rather, for macrophages, hence the name “CARMA,” closed on an initial round of funding to advance its technologies. 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
VB-111, A Novel Gene Therapeutic Agent in Cancer- Ashini R. Dias, Contributor
The formation of new blood vessels or angiogenesis is a normal process required for growth and wound healing. Unfortunately, it also plays a critically enabling role in the growth, proliferation, invasion and metastasis of cancers since tumors cannot grow beyond a certain size without a blood supply. The resulting new blood vessels feed the growing tumors with necessary oxygen and nutrients, allowing the cancer cells to invade nearby tissue, and gain access to immature blood vessels to metastasize throughout the body. Platelet Derived Growth Factor (PDGF), which is secreted by carcinoma cells, is the most important signaling molecule to stimulate and proliferate stromal cells. Myofibroblasts, transdifferentiated from stromal fibroblasts by PDGF, secretes chemokines that recruit endothelial precursor cells (EPC) in to the stroma. Myofibroblasts also secrete vascular endothelial growth factor (VEGF), which induces the differentiation of EPCs into endothelial cells, subsequently forming the neo-vasculature. Continue reading
Combined CA4P (Fosbretabulin) therapy in Cancer- Ashini R. Dias, Contributor
Malignant tumors cannot grow beyond a certain size without establishing blood supply to feed them with necessary nutrients and oxygen. The process of recruiting new blood vessels to the tumor is termed angiogenesis. Growth factors, mainly secreted by the tumor itself, induce angiogenesis; the most notable of these is vascular endothelial growth factor (VEGF), which helps endothelial precursor cells mature into neo-capillary forming, endothelial cells. These secrete other growth factors, like platelet derivative growth factor (PDGF), which attracts pericytes and vascular smooth muscle cells that, together, create the outer layers of capillaries. 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
Pancreatic cancer drug that mimics heparin halted in Phase 2 for lack of efficacy
A Phase 2 study of necuparanib (from Momenta Pharmaceuticals) was halted following an interim futility analysis. The data and safety monitoring board (DSMB) ran the analysis once 57 patients in the 120-person trial had died, leading to the conclusion that necuparanib was showing insufficient efficacy to justify continuing the study. 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