A wonderful Sunday to you, myeloma world.

We hope that, wherever you may be today, the sun is shining as brightly as it is here at Myeloma Morning Headquarters, and that the sky is as blue.

In today's Myeloma Morning ^[1], we'll be summarizing two new myeloma-related research studies. We also have “Quickly Noted” descriptions of two additional studies. Overall, there are five items in our daily list of new multiple myeloma research, which – as always – is included at the end of our report.

Both of the studies we summarize today involve laboratory research.

One examines the possibility that a common class of drugs – proton pump inhibitors – may include treatments with anti-myeloma activity.

The second study explores whether the investigational drug saracatinib (AZD0530) could be used to prevent myeloma bone disease.

Lansoprazole And Omeprazole As Potential Multiple Myeloma Therapies

We start our report today with a study by researchers at the National Institute of Health (Istituto Superiore di Sanità) in Rome, Italy. The authors examine whether drugs known as proton pump inhibitors could be used to treat multiple myeloma (abstract ^[2]).

We are guessing that most of our readers have heard of at least one drug in the proton pump inhibitor (PPI) class, and many of you are probably taking a PPI on a daily basis. PPIs are used to control stomach acidity and prevent gastroesophageal reflux, which can cause heartburn. Popular PPIs include omeprazole (Prilosec, Losec), lansoprazole (Prevacid), pantoprazole (Protonix), and esomeprazole (Nexium).

The Italian researchers investigated whether two specific PPIs – lansoprazole and omeprazole – have anti-myeloma activity. Their research was motivated by previous studies which have found that PPIs can have anti-cancer activity.

The researchers exposed multiple myeloma cells to the two PPIs in laboratory testing. They found that, even at relatively low concentrations, lansoprazole (Prevacid) killed myeloma cells. Omeprazole, on the other hand, did not.

Further investigation revealed that lansoprazole's main effect on the multiple myeloma cells was to kill them directly (via “caspase-independent apoptotic-like cytotoxicity”), rather than by reducing the rate at which the cells reproduced.

Readers should bear in mind that these are laboratory findings, and anti-myeloma activity in the laboratory very frequently does not translate into anti-myeloma activity in actual patients. We therefore look forward to further investigations of the potential anti-myeloma activity of lansoprazole.

Saracatinib (AZD0530) For Myeloma Bone Disease

Our second study today involves the drug saracatinib (AZD0350). It reports on efforts by Belgian researchers to investigate saracatinib's impact on myeloma bone disease (full text ^[3]).

Now, saracatinib is an interesting drug. It belongs to two classes of drugs, Src inhibitors and Bcr-Abl tyrosine-kinase inhibitors. Initially, saracatinib was investigated as a potential treatment for different kinds of solid (not blood) cancers.

That didn't work out.

Along the way, however, it was discovered that saracatinib might be able to treat people with Alzheimers disease, schizophrenia, and other neurological conditions. Clinical trials have therefore been initiated to test the drug in such diseases (list of open saracatinib clinical trials ^[4]).

In addition, researchers began to suspect that saracatinib could counteract myeloma bone disease (multiple myeloma's tendency to eat holes in patient's bones).

This is what the Belgian researchers decided to explore. They conducted laboratory investigations of saracatinib's effect on the two types of cells responsible for bone strength – osteoblasts and osteoclasts. They also studied the effect of the drug on myeloma bone disease in mouse models of the disease.

They found that saracatinib definitely diminishes the destructive activity of osteoclasts, the cells that break down bones as part of the constant bone destruction / bone building cycle that goes on in the body.

Saracatinib also diminishes certain activities of osteoblasts, the cells that build up bones. However, when the drug was tested in multiple myeloma mouse models, it significantly reduced the net amount of bone destruction from myeloma bone disease. “We observed a marked reduction of bone loss after treatment of multiple myeloma-bearing mice with saracatinib,” the authors write in their article.

The authors conclude by saying that, based on their findings, saracatinib – or drugs similar to it, such as AZD0424 – should be tested in multiple myeloma patients to assess whether they affect bone loss.

Quickly Noted

• An article in today's list of new research gives an overview of Darzalex ^[5] (daratumumab) and Empliciti ^[6] (elotuzumab) and research that has been published about the use of the drugs in multiple myeloma. The three authors of the article are based at Memorial Sloan-Kettering Cancer Center in New York City (abstract ^[7]).
• The 100^th anniversary annual meeting of the American Radium Society (ARS) is taking place this weekend just down the road from Myeloma Morning Headquarters, on the riverfront in Philadelphia. One of the presentations at the meeting is a small retrospective review of the use of single fraction (dose) radiation therapy for bone pain in multiple myeloma patients. The authors of the study find that single fraction therapy is effective at reducing pain and can reduce the time between radiation therapy and the start of anti-myeloma treatment (abstract ^[8]).

New Myeloma-Related Research Articles

1. Afifi, S. et al., “Immunotherapy: A new approach to treating multiple myeloma” in Annals of Pharmacotherapy, April 15, 2016 (abstract ^[7])
2. Canitano, A. et al., “Proton pump inhibitors induce a caspase-independent antitumor effect against human multiple myeloma” in Cancer Letters, April 12, 2016 (abstract ^[2])
3. Heusschen, R. et al., “SRC kinase inhibition with saracatinib limits the development of osteolytic bone disease in multiple myeloma” in Oncotarget, April 15, 2016 (full text ^[3])
4. Konjević, G. et al., “Decreased CD161 activating and increased CD158a inhibitory receptor expression on NK cells underlies impaired NK cell cytotoxicity in patients with multiple myeloma” in the Journal of Clinical Pathology, April 15, 2016 (abstract ^[9])
5. Skrepnik, T. et al., “Single-fraction radiation therapy for the treatment of multiple myeloma bony metastases provides pain control and decreases time to chemotherapy” in Oncology, April 15, 2016 (abstract ^[8])