LAM-002 is an exquisitely selective first-in-class kinase inhibitor that is cytotoxic for specific cancers with little to no effect on normal cells. LAM Therapeutics advanced LAM-002 into a Phase 1 trial in relapsed or refractory B-cell non-Hodgkin lymphoma within one year of discovery (Company Pipeline, LAM Therapeutics, APR 14, 2016, View Source [SID:1234510762]).

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LAM-002 is also being evaluated in pre-clinical models of neurological disease.

On April 14, 2016 Burzynski Research Institute, Inc. (BRI) reported that it has begun patient enrollment into an FDA-reviewed and IRB-approved, open-label, single-arm phase 2 study of Antineoplastons A10 and AS2-1 in patients > 3 months of age with a diffuse intrinsic brainstem glioma (DIPG) (Press release, Burzynski Research Institute, APR 14, 2016, View Source [SID:1234510800]). Study subjects will be placed in one of five treatment groups based on their age and whether or not they have received prior treatment for DIPG. The primary study endpoint is a decrease in the size of the tumor, either a partial response (≥ 50% decrease in the size of the tumor) or a complete response (disappearance of the tumor).

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DIPG is primarily a disease of childhood, with the majority of patients being between 5 and 10 years of age. However, infants and adults can also be affected. It is the most common brainstem tumor in children, representing 75-80% of childhood brainstem tumors, and affecting an estimated 300 children in the U.S. each year. The prognosis for children with DIPG is significantly worse than that of other primary brainstem tumors. The standard of care for patients with newly-diagnosed DIPG is radiation therapy (RT), which appears to control tumor growth for a short period of time, prolonging survival by approximately 3 months. Within 3-8 months after completion of RT, most patients with DIPG will show progression of their disease. No chemotherapeutic agent has ever demonstrated a significant improvement in outcome beyond that achieved by RT alone. An original BRI paper, "The response and survival of children with recurrent intrinsic pontine glioma based on a phase II study of Antineoplastons A10 and AS2-1 in patients with brainstem glioma" was published in Child’s Nervous System in December 2014, Volume 30, Issue 12, pages 2051-2061 (DOI 10.1007/s00381-014-2401-z).

Guidelines recommend that women with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (mBC) initiate hormonal therapy before chemotherapy. This study compared outcomes of women with mBC who received chemotherapy first versus hormonal therapy.
A retrospective cohort study of women with mBC was conducted using a large US commercial health plan database between 1/1/2008-4/30/2013. Subjects had evidence of a HR+/HER2- tumor subtype in a cancer registry and use of chemotherapy or hormonal therapy in claims. Subjects were continuously enrolled for ≥6 months after metastasis and assigned to cohorts for receiving chemotherapy only or hormonal therapy only during first-line (CT-1L vs HT-1L). Adjusted incidence rates of clinically significant events were compared using a negative binomial model, and adjusted health care costs were compared using a generalized linear model.
324 women with HR+/HER2- mBC met the selection criteria; 179 (55%) received CT-1L and 145 (45%) received HT-1L. Mortality rates did not differ between cohorts [unadjusted incidence rate ratio (IRR): 1.67, 95% CI: 0.82-3.46; adjusted IRR: 0.64, 95% CI: 0.32-1.27). Adjusted average total all-cause health care costs were $11,090 for women with CT-1L and $6,743 for women with HT-1L (cost ratio: 1.64, 95% CI: 1.36-1.99).
Observed use of first-line chemotherapy (>50%) was higher than expected given the HR+ molecular profile of the tumors. Chemotherapy use during first-line did not appear to be associated with a survival benefit but was associated with significantly higher costs compared with the use of hormonal therapy during first-line; however, this comparison is limited by demographic and baseline characteristic differences between the 2 cohorts. This study contributes to understanding real-world treatment patterns and the associated clinical and economic outcomes of using chemotherapy versus hormonal therapy as a first-line treatment option for the HR+/HER2- mBC population.

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The discovery and optimisation of novel, potent and selective small molecule inhibitors of the α-isoform of type III phosphatidylinositol-4-kinase (PI4Kα) are described. Lead compounds show cellular activity consistent with their PI4Kα potency inhibiting the accumulation of IP1 after PDGF stimulation and reducing cellular PIP, PIP2 and PIP3 levels. Hence, these compounds are useful in vitro tools to delineate the complex biological pathways involved in signalling through PI4Kα.
Copyright © 2015 Elsevier Ltd. All rights reserved.

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Ligands from the B7 family bind to receptors of the CD28 family, which regulate early T cell activation in lymphoid organs and control inflammation and autoimmunity in peripheral tissues. Programmed death-1 (PD-1), a member of the CD28 family, is an inhibitory receptor on T cells and is responsible for their dysfunction in infectious diseases and cancers. The complex mechanisms controlling the expression and signaling of PD-1 and programmed death ligand 1 (PD-L1) are emerging. Recently completed and ongoing clinical trials that target these molecules have shown remarkable success by generating durable clinical responses in some cancer patients. In chronic viral infections, preclinical data reveal that targeting PD-1 and its ligands can improve T cell responses and virus clearance. There is also promise in stimulating this pathway for the treatment of autoimmune and inflammatory disorders.
Copyright © 2015 Elsevier Ltd. All rights reserved.

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