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Repurposing tofacitinib as an anti-myeloma therapeutic to reverse growth-promoting effects of the bone marrow microenvironment

The myeloma bone marrow microenvironment promotes proliferation of malignant plasma cells and resistance to therapy. Activation of JAK/STAT signaling …

Clinical Trials

Medscape Log In

Medscape Log In

Medscape Log In

10 Reasons to Take a European River Cruise

There are so many ways to travel around Europe and no doubt you’ve tried some of them already. You can take cheap flights, take the trains or even …

Free Registration

25-05-2018 | Colorectal cancer | News<p>The presence of the <i>BRAF</i> V600E mutation in colorectal liver metastases is associated with a worse prognosis and …

ASCO 2016: Locoregional Surgery Followed by Standard Therapy Improves Survival vs Standard Therapy Alone in Stage IV Breast Cancer

By The ASCO Post<br>Posted: 6/4/2016 2:04:33 PM<br>Last Updated: 6/4/2016 2:04:33 PM <br>Tweet this page<p>Advertisement<p>Key Points<p>At about 40 months after …

Garden Design Magazine 2016

Detroit Garden Works has been on hiatus since January 15. Anyone who comes to our door is welcome to come inside, but most of what there is to see …

4 stocks to own for the next year

After a rough start for markets in 2016, "Fast Money" traders looked ahead to what they would want to own in a year.<p>Worries of an economic slowdown …

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Better Homes & Gardens Home

Our free Planting Guide for this garden includes a larger version of the illustration, a detailed layout diagram, a list of plants for the garden as …

Plants

This is what the end of the 'great credit bubble' looks like

Investors, lured into the $1.8-trillion US junk-bond minefield by the Fed's siren call to be fleeced by Wall Street and Corporate America, are now getting bloodied as these bonds are plunging.<p>Standard & Poor's "distress ratio" for bonds, which started rising a year ago, reached 20.1% by the end of …

Markets

Why manicured lawns should become a thing of the past

Many folks, not to mention homeowners associations, cling to that model of the American yard as one of clipped foundation shrubs, groomed lawns and trees with mulch circles. Naked soil must be blanketed spring and fall with shredded mulch. Fallen leaves are treated as trash.<p>The real gardening world …

How the Little Known Nutrient Alpha Lipoic Acid Kills Cancer Cells and Outperforms Chemotherapy

Alpha lipoic acid (ALA) is a virtually unknown nutrient. It is a naturally occurring thiol antioxidant, or simply stated, a sulfur containing …

Wellness

Atezolizumab Again Achieves Phase II Success in PD-L1-Positive Lung Cancer

Sandra Horning, MD<p>Atezolizumab (MPDL3280A) met the primary endpoint of objective response in PD-L1–positive patients with advanced non–small cell …

Diversify the tax structure of your retirement investments

This article is reprinted by permission from NextAvenue.org.<p>The standard—and very good—advice about retirement savings is to maximize your …

Retirement

ASCO 2015: Latest in chronic lymphocytic leukaemia. ASCO 2015: Latest in chronic lymphocytic leukaemia. Oncology videos for healthcare professionals

Prof Stephan Stilgenbauer and Dr Jacqueline Barrientos<p>Prof Stilgenbauer (Universitätsklinikum Ulm, Ulm, Germany) and Dr Jacqueline Barrientos (LIJ …

#DrPardoll tumors PROTECT themselves by expressing PD-L1 #asco15 #immunotherapy #ascoexperience

PHILADELPHIA — MEHD7945A, a dual-action antibody that targets two members of the epidermal growth factor receptor (EGFR) family, was found to be safe and showed clinical activity in some patients with locally advanced or metastatic refractory epithelial cancers, including cancers of the head and neck, according to phase I clinical trial data published in Clinical Cancer Research, a journal of the American Association for Cancer Research (AACR). “MEHD7945A is a humanized IgG1 antibody that has the capacity to target two members of the EGFR family, EGFR [also known as HER1] and HER3,” said José Baselga, MD, PhD, physician-in-chief and chief medical officer at the Memorial Sloan Kettering Cancer Center in New York.Baselga, who is also president of the AACR, explained, “For about 20 years, we have been working on the hypothesis of targeting EGFR in epithelial cancers as a fruitful approach based on our understanding that dysregulated EGFR plays an important role in tumorigenesis. What we have learned since then is that there are other players in the EGFR family, such as HER3, which are functionally similar to EGFR and, therefore, have a significant role in tumor promotion. We felt it is important that we hit not just EGFR alone, but also target HER3, with the goal of achieving more durable responses.”Binding of growth factors to EGFR and HER3 in a cell leads to activation and downstream signaling to promote cell growth. Dysregulated EGFR and/or HER3 can lead to overactive signaling, causing uncontrolled cell growth and proliferation, as seen in a variety of epithelial cancers. MEHD7945A has two antigen-binding arms, and they bind to unique targets on HER3 and EGFR, thus inhibiting the activity of multiple cancer signaling pathways.“In a phase I clinical trial, we found that MEHD7945A was well tolerated as a single agent, and we were able to confirm partial responses in patients who had refractory disease, which clearly suggests that this dual-targeting approach is a good strategy moving forward,” Baselga added.Baselga and colleagues enrolled 66 patients at six sites in the United States and Spain: 30 patients to the dose-escalation study and 36 to the dose-expansion study. All patients had received prior systemic therapies, and about 50 percent of them had received prior anti-EGFR therapies. Patients had incurable, locally advanced, or metastatic epithelial cancer, including colorectal, non-small cell lung, or head and neck cancers, which had progressed despite prior therapies.Six different dose levels were tested in the dose-escalation study, and patients enrolled in the dose-expansion study received 14 mg/kg b.w. of the drug intravenously, every two weeks until patients experienced toxicity or disease progression.No dose-limiting toxicities or drug-related grade 4 adverse events were reported in the dose-escalation or the dose-expansion cohorts. Two patients with squamous cell carcinoma of the head and neck (in the tongue and larynx, respectively) had partial responses, and eight patients had stable disease that lasted for 16 weeks or longer.   Patients whose tumors had high levels of the growth factor heregulin, which binds to EGFR, were found to benefit from the drug, according to Baselga. “Presence of high levels of the ligand [heregulin] could be a marker of response to this drug, but this needs further confirmation,” he said.“We have been using antibodies to treat cancers for a while now, but recent advancements in technology are allowing us to use antibodies in a way we have not done in the past,” Baselga noted. “Dual targeting of HER2 and HER3 was shown to be a promising strategy for breast cancers; this study adds further support to the dual-targeting approach, and also speaks to the increasing opportunities we all have with engineering antibodies for patient benefit.”This study was funded by Genentech. Genentech was involved in the study design, data interpretation, and the decision to submit for publication in conjunction with the authors. Baselga has an advisory board membership from Genentech.

Cancer

Nivolumab Regimen Significantly Improves PFS in Frontline Melanoma

Jedd Wolchok, MD, PhD<p>Frontline nivolumab more than doubled progression-free survival (PFS), both as monotherapy and combined with ipilimumab compared …

Round-up of the latest research on lung cancer. Round-up of the latest research on lung cancer. Oncology videos for healthcare professionals

Dr James Spicer - Guy's Hospital, London, UK<p>Dr Spicer talks to ecancertv at ASCO 2015, about the progress of recent drug development in lung cancer …

Novel JAK inhibitor pacritinib proving effective for easing symptoms of myelofibrosis. Novel JAK inhibitor pacritinib proving effective for easing symptoms of myelofibrosis. Oncology videos for healthcare professionals

Dr Ruben Mesa - Mayo Clinic Cancer Center, Scottsdale, USA<p>Dr Mesa talks to ecancertv at ASCO 2015 about findings from the PERSIST-1 study of patients …

ASCO 2015: Report from Day 1

Greetings from Chicago! I am here in the Windy City for the annual meeting of the American Society of Clinical Oncology (ASCO), and will be providing …

Dovitinib Shows Activity in Advanced Endometrial Cancer

the Cancer Therapy Advisor take:<p>Second-line dovitinib in <i>FGFR2</i>-mutated and <i>FGFR2</i>-non-mutated advanced or metastatic endometrial cancer had single-agent …