UCLA scientists unlock protein that can accelerate recovery in cancer patients following radiation and chemotherapy

Scientists from UCLA’s Jonsson Comprehensive Cancer Center (JCCC) have shown for the first time how a unique protein found in human bone marrow can drive stem cells to repair our blood system after an injury. These groundbreaking findings provide a roadmap to make existing radiation and chemotherapy treatments more effective for patients with cancer and other blood-related diseases.

Led by Dr. John Chute, UCLA professor of hematology and radiation oncology and JCCC member, the nearly two-year study was published online ahead of print in the Journal of Clinical Investigation.

Millions of cancer patients worldwide currently receive some form of radiation therapy or chemotherapy in hopes of curing the disease, and most will suffer damage to the blood system as a result. Current therapeutic regimens are also cyclical (generally requiring a 30-day wait period between treatments) to allow the blood system time to heal and repair.

Hematopoietic stem cells (HSCs) are cells in our body that can change and become any other type of blood cell (such as red or white blood cells). Scientists have long used HSCs in the laboratory to study how the bone marrow in our body can regulate and instruct these blood stem cells to regenerate and repair themselves, and thus help our bodies to recover after an injury or stress (such as following radiation or chemotherapy).

In his prior research, Dr. Chute discovered that specific cells that make up the lining of blood vessels in our bone marrow (called endothelial cells) play a key role in telling HSCs how to renew and repair themselves. He further theorized that following an injury or stress to our body, the blood system as a whole will benefit as the activities and functions happening in our bone marrow directly drive HSCs to promote and accelerate recovery.

In this new study, Dr. Chute and colleagues built upon their research to specifically identify a new protein called pleiotrophin. They discovered that the protein binds to HSCs, and that it is this process that activates recovery of blood stem cells and our entire blood system.

Dr. Chute’s team conducted experiments in mouse models to administer pleiotrophin after a normally lethal dose of radiation. Results showed that HSCs and the blood system recovered faster, and in two thirds of the cases the animal survived.

Additionally, Dr. Chute’s team found in further testing that by doing the opposite and actually blocking pleiotrophin (thereby preventing it from functioning), the blood stem cells saw no advantage in recovery. This highly suggests that the protein is key in accelerating recovery of the blood system.

“We have now discovered the mechanism by which pleiotrophin can instruct blood stem cells to regenerate,” said Dr. Chute. “By modeling it for potential use in human patients, this opens the door for tremendous therapeutic possibilities.”

Dr. Chute and his team are currently pursuing a Phase I clinical trial, with the goal of accelerated recovery for patients undergoing all types of radiation and chemotherapy as well as lessened delays between treatments.

“With this discovery, we hope to provide the basis for improving outcomes for patients with cancer or other blood-related diseases and who are undergoing highly toxic treatments,” said Dr. Chute.

This research was supported by funding from the National Institute of Allergy and Infectious Diseases and National Heart, Lung, and Blood Institute. Additional funding was provided by the UCLA Broad Stem Cell Research Center.

http://www.medicalnewstoday.com/releases/283036.php

 

 

Combined therapy improves survival for patients with liver cancer who are not suitable for surgery

The mature results from a trial conducted by the Asia-Pacific Hepatocellular Carcinoma Trials Group led by the National Cancer Centre Singapore (NCCS) and Singapore General Hospital (SGH) have shown that patients who suffer from inoperable advanced hepatocellular carcinoma (HCC) may have a chance to live significantly longer by using a combined therapy.

The multi-centre phase II clinical trial was conducted at four Asia Pacific tertiary medical centres to evaluate the efficacy of combining two existing treatment modalities, Sorafenib and Selective Internal Radiation Therapy (SIRT). The combination therapy involves starting patients on SIRT using SIR-Spheres microspheres, a medical device that contains radioactive microspheres labeled with yttrium-90 for short range high energy radiation therapy, followed by systemic therapy with an oral chemotherapy drug, Sorafenib, 14 days later.

The mature results of the trial published recently in a peer-reviewed journal, PLOS ONE, show that median overall survival was 20.3 months for patients with intermediate stage HCC and 8.6 months for patients with advanced liver cancer. These final results were better than the preliminary data released in 2010.

Led by Prof Pierce Chow, Senior Consultant Surgeon at NCCS and SGH, the investigator-initiated trial, which commenced in June 2008, recruited 29 patients from four countries namely Malaysia, Myanmar, Singapore and South Korea.

“Hepatocellular carcinoma is the most common type of liver cancer with limited treatment options. About 1 million individuals are diagnosed with the condition annually and only 20 per cent of them are eligible for potentially curative treatment. This is a major concern and we aim to change that,” said Prof Chow.

“It is through collaboration with hospitals and medical centres in the region that we can further our understanding of this disease that is so prevalent in the Asian population. This multi-centre phase II clinical trial, which showed that the combination therapy improves survival, is an example of how patients can benefit from the collaboration.”

The trial also revealed that median time to progression was 15.2 months and 9 months for patients with locally advanced HCC and patients with metastatic liver cancer respectively. This means that patients are able to enjoy better quality of life for a longer period, from the time therapy starts till the disease progresses.

The results of the trial also compare favorably with the known outcomes of current monotherapy treatments such as the overall survival following transarterial embolization in Asia-Pacific patients with intermediate or advanced HCC (median 18.2 and 6.8 months, respectively).

“This is an improvement of the initial result in 2010, which were already better than treatment with either therapy alone. It is very encouraging as it justifies our perseverance in seeking a deeper understanding of how we can treat this form of cancer to achieve the best results for our patient, ” said Prof Soo Khee Chee, Director of NCCS who is also involved in the Phase II study.

The trial also demonstrated that patients with locally advanced HCC can also be downstaged to receive potentially curative treatment. In the trial two patients were downstaged to receive radio-frequency ablation. Outside of this phase II trial, four other clinical patients became amendable to surgery after treatment with SIRT and another became amendable to liver transplantation after receiving combination SIRT and sorafenib therapy. Potentially curative treatment such as surgical resection, transplantation and radiofrequency ablation are otherwise not options for patients with advanced HCC. If left untreated, they have a median survival of about 4 to 8 months.

HCC, a form of liver cancer, is the 5th most common cancer worldwide. Almost 80 per cent of HCC cases are found in the Asia-Pacific region. As the majority of patients with liver cancer do not develop any symptoms, only one in five of them can potentially be cured by surgery when diagnosed.

In view of the success of the phase II trial, the phase III multi-centre trial has commenced to determine if SIRT would help patients survive longer and would potentially be the first line therapy for advanced HCC.

http://www.medicalnewstoday.com/releases/282225.php