Valstar (valrubicin), the last drug approved for the treatment of superficial bladder cancer that is refractory to front-line therapy with BCG (bacillus Calmette-Guerin), entered the market in 1998. The registration study for Valstar demonstrated a twenty percent complete response rate three months following six weekly intravesical (transurethral administration into the bladder) instillations of the novel anthracycline in patients with BCG-refractory carcinoma in situ of the bladder. Continue reading
Author Archives: Joseph Gulfo
Losing 10 pounds or more confers lower risk of endometrial cancer
The link between endometrial cancer and obesity is the strongest of all cancers studied; obesity is also strongly linked to breast and colon cancer. In the Iowa Women’s Health Study, patients who intentionally lost at least 20 pounds demonstrated a risk of endometrial cancer equivalent to non-obese patients. A supplemental analysis suggested that intentional loss of 10 pounds also reduced risk. 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
Autoimmune toxicity on checkpoint inhibitors is associated with better responses
Cancer and autoimmune disorders are opposite sides of the same coin – cancer is a result of hypo-active immunity, whereas, autoimmune diseases is the result of hyper-active immunity. This is dramatically illustrated in examining side effects in patients with melanoma who receive checkpoint therapy with ipilimumab (Yervoy), which acts in the early stages of T-cell activation and priming, and nivolumab (Opdivo), which acts in the later stages of T-cell activation in the tumor microenvironment. Continue reading
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
BMS and PsoOxus collaborate on transgenic oncolytic virus plus nivolumab
BMS paid PsiOxus $50MM upfront for exclusive rights to develop PsiOxus’ NG-348 enadenotucirev, a systemically administered oncolytic adenovirus therapeutic, in combination with Bristol-Myers Squibb’s Immuno-Oncology checkpoint inhibitor Opdivo (nivolumab) to treat a range of solid tumor types in late-stage cancer patients. This is a “big deal” – PsiOxus could receive up to $886 million in development, regulatory, and sales-based milestones, plus sales royalties. 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