A New Option For Lung Cancer Patients

 Lung Cancer is the second highest cause of cancer-related mortality in the United States, the third deadliest Cancer in the United Kingdom, and the leading cause of death out of all cancers worldwide.1 Those that are diagnosed with lung cancer generally have limited healthcare options, their best chances being chemotherapy, radiotherapy, or surgery. However, those diagnosed with metastatic lung cancer have even fewer options in terms of treatment, as after multiple doses of chemotherapy alongside drugs like cisplatin and pemetrexed, patients showing no improvement are usually are directed down the path of palliative care, and are generally and in most cases can only hope to have their time left to increase by a few months if they are lucky2. Recently in the United Kingdom, fifty-six of these patients with the odds completely against them have been given a chance at remission.

The image above shows how MSC’s with overexpressed TRAIL proteins can cause tumor suppression in cancerous cells.

           

Researchers and students at the University College of London have been collaboratively working together to design a therapy that will target tumor cells in lungs and prevent them from metastasizing. They have experimented with their innovative therapy on mice and have seen promising results where lung masses have been shrunken or eliminated within the organism.2 This therapy is unique however, as it combines stem cell and gene therapies to target the cancerous cells. Dr. Sam Janes, leader of the study speculates. “If clinical trials are successful, our treatment could be transformative for the treatment of lung cancer, and possibly other types of tumor in future.”3 The team’s approach is to take stem cells from bone marrow, known as mesenchymal stem cells, and to modify their genome in order to overexpress a tumor-suppressing gene called TRIAL (tumor necrosis factor-related apoptosis-inducing ligand).

The mesenchymal stem cells used in this study are generally found in the bone marrow but can be found in other structures such as cord and peripheral blood, fetal lung and liver tissues, and in the fallopian tube. They can be differentiated into chondrocytes (produce and maintain healthy cartilage), osteoblasts (bone formation), or adipocytes (i.e. lipocytes or fat cells). Morphologically, these cells have a long slender structure4 that assists the cell in its programmed pursuit of penetrating cancer cells in the lungs. They also have a larger than normal nucleus full of programmable genes such as TRIAL. The university study found that “When administered to mice with mesothelioma, the stem cell-gene therapy combo was associated with a drop in tumor burden and an uptick in the apoptosis process that is triggered by the TRAIL protein.”5 One huge advantage of this treatment is that the cells injected in vitro do not trigger an immune response from the body because they lack certain proteins on their outer surface; “They do not possess any unique markers for their identification, so their identification relies on the expression of CD73, CD90 and CD105 while lacking CD34, CD45 and other haematopoietic stem cell markers”.6 This lack of protein expression on their membranes increases the chances the stem cell will reach its desired target before the body can recognize and denature its proteins.

Different mesenchymal stem cells, both human and mouse multipotent stem cells, were injected into mice with malignant mesothelioma and showed successful but varied results in how susceptible the cells were in infiltrating the tumor. Essentially these stem cells are programmed to overexpress this TRAIL protein which targets and binds to death receptor proteins that are expressed primarily on malignant cells.7 Significantly, the study also found that the overexpression of TRAIL was most effective on the tumor cells when combined with chemotherapy.8 The mesenchymal stem cells also have an anti-inflammatory property which has been hypothesized to aid with the tumor suppressing process alongside the overexpression of the TRAIL protein however it has yet to be proven.

The fact that this therapy is now safe enough to test in humans is remarkable. The future of treating severe conditions like lung cancer is dependent on scientists like those at the University College of London who bring innovative and creative ideas to the lab and turn them into procedures that can be used within the body. Being the first stem cell-gene therapy trial, this procedure of overloading your system with an army of billions of stem cells provides much hope to those 1.6 million people who are projected to die from lung cancer next year10. In the past few years lung cancer has caused more deaths than breast, colon, and prostate cancer combined. The scientists at UCL recognized this and are well on their way to finding an effective cure.

(Go to http://www.futuretimeline.net/blog/2015/03/7.htm#.VQJCAzqM7ww for a GIF of the stem cells attacking and invading malignant mesotheliomas in mice)

References

1. http://www.cancer.gov/statistics
2. http://www.theguardian.com/society/2015/mar/06/lung-cancer-stem-cell-therapy-trial-uk
3. http://news.sky.com/story/1439915/experimental-lung-cancer-therapy-trial-for-uk
4. http://www.rndsystems.com/molecule_group.aspx?g=805
5. http://www.fiercebiotech.com/story/uk-academics-move-cell-gene-lung-cancer-therapy-clinic/2015-03-11
6. Dominici M, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006(8):315–317.
7. Holoch PA, Griffith TS. TNF-related apoptosis-inducing ligand (TRAIL): a new path to anti-cancer therapies. Eur J Pharmacol 2009; 625: 63–72.
8. Crino L, Foglietta J, Hamzaj A. Development of new first-line therapeutic options for non-small-cell lung cancer. Lung Cancer. 2006(54):S19–S24.
9. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3929000/
10. www.who.int/