Author Archives: Joseph Gulfo

Regorafenib approved for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a primary cancer of the liver that occurs as a result of chronic liver disease, including cirrhosis and hepatitis B and C infections (Figure 1). Serum alpha-fetoprotien (AFP) levels are elevated early in the disease, and screening of patients with chronic liver disease for AFP has lead to earlier diagnosis of HCC. The test is 40-64% sensitive (the ability to detect disease when disease is truly present) because many HCCs do not produce AFP, but it is 75-91% specific (the ability to rule out disease when disease is truly absent) – an AFP of over 400 mg/mL is considered diagnostic. Continue reading →

Inhibition of Nuclear Export Protein XPO1 in Cancer

Selinexor (KPT-33) is a drug that inhibits exportin 1 (XPO1 and CRM1), a nuclear transport protein that shuttles nuclear proteins through the nuclear pore and is responsible for the removal of proteins from the nucleus: 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 →

PD-L1 Inhibitor, avelumab, approved for Merkel cell carcinoma

Avelumab (Bavencio) is a PD-L1 inhibitor that was approved for the treatment of patients with metastatic Merkel cell carcinoma (MCC). 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 →

Hyperprogression on Checkpoint Inhibition Immunotherapy

Results with checkpoint inhibitors nivolumab (PD-1, Opdivo), pembrolizumab (PD-1, Keytruda), and atezolizumab (PD-L1, Tecentriq) are impressive. Some patients have experienced incredible and prolonged responses. These drugs are truly modern medical breakthroughs.
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Ublituximab, a novel anti-CD20 Monoclonal Antibody for CLL

TG Therapeutics is developing ublituximab, and anti-CD20 monoclonal antibody for patients with CLL (Chronic Lymphocytic Leukemia). In a phase 3 study in patients with relapsed disease, the combination of ublituximab and ibrutinib (Imbruvica) was superior to ibrutinib, alone – the overall response rates were 80% and 47%, respectively. Continue reading →

Juno Advances CAR T-cell CAR017 and Halts CAR015 in Non-Hodgkin Lymphoma

Juno Therapeutics is developing Chimeric Antigen Receptor (CAR) T-cells directed against B-cell antigen CD19 for the treatment of patients with B-cell lymphomas. The company has elected to halt the development of JCAR015 for Acute Lymphoblastic Leukemia (ALL) and proceed with JCAR017 for relapsed/refractory diffuse large B-cell lymphoma (DLBCL), the most common form of Non-Hodgkin Lymphoma (NHL), due to the development of cerebral edema and subsequent death of several patients with ALL enrolled in its phase 2 ROCKET trial, which has been suspended. Continue reading →

Argos’ Phase 3 Metastatic Renal Cell Carcinoma Study Discontinued by Data Monitoring Committee

Rocapuldencel-T is an autologous dendritic cell immunotherapy for patients with metastatic renal cell carcinoma about which we have written previously. It is produced by isolating patient tumor mRNA, which is then electroporated into patient dendritic cells in the presence of CD40 ligand. The rationale of this approach is to bypass mechanisms by which cancer cells dampen the anti-tumor immune response, including down-regulation of MHC Class I molecules. If the cancer antigens are presented on licensed dendritic cells, logically, the immune system would be appropriately stimulated to attack the cancer. Continue reading →