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
Category Archives: Uncategorized
PD-L1 Expression correlates with outcomes in patients with melanoma
Keytruda (pembrolizumab) and Opdivo (nivolumab) are monoclonal antibodies that disrupt the PD-1 (Opdivo) / PD-L1 (Keytruda) pathway; they are approved by the FDA for the treatment of patients with unresectable melanoma, as well as other cancers including non-small cell lung cancer (NSCLC), head and neck cancer, renal cell carcinoma (Opdivo), and Hodg kin lymphoma (Opdivo). Keytruda is limited to patients with NSCLC with a tumor proportion score (TPS) of greater than 50% for PD-L1 staining. Continue reading
CDK4/6 Inhibitors – Excellent Results Support Paradigm Shift in HR+/HER2- Breast Cancer
We have previously written about CDK4/6 inhibitor, palbociclib (Ibrance) for the treatment of patients with hormone receptor positive (HR+) Her-2 negative (HER2-) disease. In a randomized study of 165 patients who had not been treated previously, palbociclib plus letrozole (a nonsteroidal competitive inhibitor of the aromatase enzyme system that inhibits the conversion of androgens to estrogens) was superior to letrozole, alone: 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
Xencor’s Bispecific Antibodies in AML and B Cell Malignancies – Ashini R. Dias, Contributor
Most of the antibodies currently used in therapy are monospecific or monoclonal – they specifically target a particular part of an antigen, called an epitope. The heterogeneous nature of the cancer allows frequent mutations and cross-talk among multiple signaling cascades, which ultimately leads to uncontrollable growth and proliferation of the tumor. Thus, antibodies that bind to two different epitopes on the same or different antigens (known as bispecific) are conceptually superior to monoclonal antibodies. The “dual-target” functionality of the bi-specific antibody consisting of two variable domains allows it to bind to multiple surface receptors or ligands in signaling pathways. Although this phenomenon was identified 30 years back, the first bispecific antibody [Removab – catamuxumab: binds to epithelial cell adhesion molecule (EpCAM) on tumor cells the CD3 antigen on T-cells] was approved for therapy in 2009 in Europe for the treatment of malignant ascites after long years of research and development. Continue reading
NQ01 – a new target for cancer therapy
NQO1 [NAD(P)H:quinone oxidoreductase 1 over-expression has been shown to confer a poor prognosis for patients with cancer of the breast, colon, cervix, lung and pancreas. Recent research indicates that the mechanism involves stabilization HIF-1α (hypoxia inducible factor-1) such that it is not degraded. Continue reading
Tagrisso is superior to platinum-based chemotherapy for patients with relapsed lung cancer following front-line anti EGFR therapy
Tagrisso (osimertinib) is a kinase inhibitor indicated for patients with metastatic epidermal growth factor T790M mutation-positive lung cancer. It was approved under accelerated approval provisions in November 2015 on the basis of phase 2 trials demonstrating a combined overall objective response rate of 59%. Continue reading
Neratinib for breast cancer – the key is managing gastrointestinal toxicity
Neratinib is an irreversible tyrosine-kinase inhibitor of EGFR (epidermal growth factor receptor), as well as HER1, HER2, and HER4. It is being developed for patients with breast cancer. It blocks many signal transduction pathways that result in proliferation and invasion, leading to cell cycle arrest and apoptosis. (Figures 1 and 2). Continue reading
Engineering safety into CAR T-cells to address toxicities
Adoptive immunotherapy with engineered T-cells, for example, CAR T-cells (Chimeric Antigen Receptor) is associated with significant toxicities including cytokine release syndrome, neurologic toxicity, “on target/off tumor” recognition, and anaphylaxis. CAR T-cells lack the ability to respond to signals that maintain immune homeostasis. For this reason, they are effective relentless killers of cells that express the target to which they have been programmed, however, at a safety cost. Continue reading
Opdivo combined with novel IL-2 prodrug immune stimulant
Bristol Myers Squibb (BMS) and Nektar Therapeutics announced a collaboration in which BMS’ PD-1 checkpoint inhibitor (Opdivo, nivolumab) will be combined with Nektar;s CD-122 agonist NKTR-214. Continue reading