Pancreatic cancer – early detection, immune response, and infection-based resistance

Approximately 1.6 percent of men and women will be diagnosed with pancreatic cancer at some point during their lifetime. In 2014, an estimated 64,668 patients were living with the disease. The five-year survival for pancreatic cancer is 8.2% and it is projected to be the second leading cause of death due to cancer (behind lung cancer) in the US by the year 2030. For good reason, then, November is Pancreatic Awareness Month. Several recent research items are of particular interest to us. Continue reading

Using a blood test to select patients most likely to respond to checkpoint therapy

Checkpoint therapy with PD-(L)1 and CTLA4-directed monoclonal antibodies has shown to be extremely effective for many patients with a variety of tumors. PD-1 testing, alone, however, are lacking in selecting patients for therapy – up to 17% of patients who do not meet criteria for PD-1 positivity respond to treatment, and many patients with PD-1 tumors do not respond well to checkpoint therapy. Continue reading

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

Early discontinuation of checkpoint inhibition due to immune-related side effects does not have a significant impact on treatment efficacy

A course of treatment with checkpoint inhibitors Yervoy (ipilimumab) and Opdivo (nivolumab) for patients with unresectable or metastatic melanoma is every 3 weeks for a total of four doses. Almost forty percent of patients receiving this combined regimen discontinue treatment because of  immune-related adverse events. 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

Priming cancer for immunotherapy

Augmenting the responses to checkpoint inhibitors, which remove the “breaks” from the immune response, is a very popular area of research. The general concept is to turn immunologically cold tumors hot. For example, triple negative breast cancer (TNBC) is considered an immunologically cold tumor – anti-PD(L)1 therapy has shown responses of just 5-10%. Continue reading

Anti-APRIL Antibody BION-1301 for Multiple Myeloma

Multiple myeloma (MM) is a cancer of plasma cells in the bone marrow. Plasma cells are B lymphocytes (B-cells) that have been activated to produce immunoglobulins. When plasma cells become cancerous, the produce copious amounts of immunoglobulins and proliferate in the bone marrow, causing crowding-out of other essential hematopoietic cells, leading to reduced numbers of functioning white blood cells (leukopenia leading to immunosuppression), red blood cells (anemia), and megakaryocytes (thrombocytopenia). Continue reading

CLEC12A – a novel target for AML and MDS

CLEC12 (C-Type Lectin Domain Family 12 Member A) is negative regulator of granulocyte and monocyte functioning. It is a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. It is also known as Myeloid Inhibitory C-Type Lectin-Like Receptor and Dendritic Cell-Associated Lectin. CLEC12 is a cell surface receptor that modulates signaling cascades and mediates tyrosine phosphorylation of target MAP kinases. Continue reading

Sitravatinib plus nivolumab in NSCLC

Sitravatinib (MGCD516) is an oral multi-tyrosine kinase inhibitor being developed by Mirati Therapeutics. Last week, the company announced that three of eleven patients with non-small cell lung cancer (NSCLC) with genetic alterations in MET, AXL, RET, TRK, DDR2, KDR, PDGFRA, KIT or CBL who were resistant to checkpoint [anti PD-(L)1 therapy] had confirmed partial responses; because of this, dosing in the 34-patient expansion cohort will proceed. Continue reading

Opdivo and Yervoy, the new front-line standard for poor/intermediate-risk renal cell carcinoma

The results of CheckMate 214 demonstrated that combination checkpoint immunotherapy with nivolumab (Opdivo; anti-PD-1 monoclonal antibody) and ipilimumab (Yervoy; anti-CTLA-4 monoclonal antibody), is superior to sunitinib (Sutent; multikinase inhibitor) in the treatment of patients with newly diagnosed renal cell carcinoma (RCC). Interestingly, prior to sunitinib, another immunotherapeutic approach – interferon-alpha (IFN-α) – was the front-line treatment of choice for renal cell carcinoma, which, like melanoma, is very immune-responsive. Continue reading