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ОглавлениеClinical Trials, U.S.: Solid Tumors
Clinical Trials, U.S.: Solid Tumors
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Clinical Trials, U.S.: Solid Tumors
Cancer arises when a cell starts to divide in an abnormal, unregulated way and ends up forming a tumor. Solid tumors are defined as masses of abnormal tissue located in soft tissues or in organs devoid of fluid cysts. Harmless tumors do not contain cancerous cells and are therefore called benign, whereas dangerous tumors bear cancerous cells and are called malignant. Depending on where in the body they grow, tumors are called “solid” or “liquid.” More than 80 percent of all cancers are caused by solid tumors arising in a tissue, an organ, or a gland. Common sites for solid tumors are lungs, breasts, colon, prostate, brain, pancreas, skin, uterus, and liver.
With the growing incidence of cancer in the world and in the United States, there is an evident need to find better treatments for cancer tumors in general and for solid tumors in particular. Years of research and clinical trials in solid tumors have paved the way for researchers and scientists to test whether stem cell transplantation could benefit such conditions in a dramatic way. Clinical trials are constantly under way to test novel therapies that use stem cells in patients who do not respond to standard treatments.
The Nature of Solid Tumors
Solid tumors are further divided into sarcomas, lymphomas, and carcinomas, based on the cell types involved: sarcomas develop in cartilage, bone, muscle, fat, connective tissue, or blood vessels. Lymphomas are tumors of the lymphatic system. And carcinomas are tumors covering internal organs or growing in skin cells. Benign solid tumors can usually be removed and do not pose any long-term threat. Conversely, malignant tumors possess aggressive properties and can easily metastasize via blood or the lymphatic system, a harbinger of poor prognosis for the patient.
Why Do Solid Tumors Appear?
While it is true that cancer runs in families, only a minority of cases are caused by an inherited defective gene. Usually, the abnormal growth and treatment resistance of the majority of cancers are caused by irregularities in a patient’s gene sequence, or in gene regulation. Such deficiencies are usually acquired, rarely inherited.
Staging plays an important role in cancer diagnosis as it helps make therapeutic decisions based on historical data of specific outcomes after treatment. A combination of factors—size of tumor, number of lymph nodes, and whether metastases can be detected—provide details on the overall stage of the cancer, which is ranked from 0 to IV. The patient’s age and health status also influence the tumor prognosis.
Treatment
The standard of care sustaining the current treatment of solid tumors includes surgery, chemotherapy, and radiation. Surgery is known to be the treatment of choice for localized and treatable tumors. Chemotherapy, often combined with surgery and radiation, helps destroy cancer cells and extends a patient’s life. As for radiation, its main purpose is to shrink the tumor as much as possible prior to removal. A corollary outcome is the fact that administration of radiation prevents the recurrence of the tumor.
There is no doubt that surgery, chemotherapy, and radiation treatments offer valuable benefits to cancer patients; however, some of these therapies are debilitating, toxic, and occasionally lethal. Attempts to alleviate these side effects have led scientists to develop more targeted treatments, such as immunotherapy. In immunotherapy, tumor cells are exposed to powerful agents that suppress the tumor, or are tagged with specific beacons that trigger the immune system into targeting a tumor for elimination. In cell-based immunotherapies, the patient receives, via infusion, subsets of immune system cells that tackle and kill the affected cells. Hematopoietic stem cell transplantation is the most common type of cell therapy currently in use.
Although technological progress keeps refining the set of treatment options and newer therapeutics are being tested—cancer vaccines, molecular testing, or cytokine-based therapies—the bulk of metastatic solid tumors remain incurable.
Can Stem Cells Win the Fight Against Solid Tumors?
Hematopoietic stem cell transplants (HSCTs) have been used for years to resupply blood cells in patients who have received cytotoxic agents (such as radiation or chemotherapy). The clinical use of hematopoietic stem cells (HSCs) dates back to the 1950s, when the first transplant was carried out in an effort to cure a lethal form of leukemia. The idea back then was to eradicate the leukemic cells through radiation and then transplant the normal hematopoietic stem cells to regenerate blood. In the 64 years that followed, scientists became greatly convinced of the importance of correctly matching donors to recipients and of the increasing need to manage subsequent complications arising from the transplantation procedure.
With this in mind, researchers and clinicians have leveraged their knowledge and applied it to the treatment of other blood conditions as well as solid tumors. Today, hematopoietic stem cell transplants are being routinely administered as an adjuvant therapy to radiation and chemotherapy. Unfortunately, in spite of these recent advances, more than 50 percent of patients are still not cured.
Autologous and Allogeneic HSCTs
HSCTs can be transplanted in two ways: either through stem cells originating from the patient (autologous) or through stem cells coming from a donor (allogeneic). Allogeneic HSCTs show proven benefits, such as their ability to kill existing tumor cells in the recipient. This occurrence, labeled graft versus tumor (GVT), is an important feature of allogeneic transplants. When combined with chemotherapy, allogeneic transplants have succeeded in decreasing the rate of relapse in solid tumors affecting kidneys and breasts. Autologous HSCTs can be administered to patients with solid tumors and reduce the possibility of graft rejection. This treatment option is very useful in young children who cannot undergo radiation, and the fact that they can be re-infused with their own hematopoietic stem cells is a plus.
Hematopoietic Stem Cell Transplants and New Demand
As people get old, the risk of incurring solid tumors increases, therefore creating a greater demand for hematopoietic stem cell transplants to shield patients from the noxious effects of radiation and chemotherapy. Because of the shortage of donor-recipient bone marrow around the world, researchers have been looking into ways to find other types of stem cells that could constitute sustainable sources of hematopoietic transplants.
One potential option might reside in the use of umbilical cord blood. One of the benefits of cord blood is that its supply is simple, and it does not create any risks to donors. Another advantage is the diminished likelihood of virus transmission; and finally, there would be no ethical issues related to its use. The only drawback is the limited quantity of stem cells available per umbilical cord, which is barely enough to provide treatment to a child or an adult of small size. Such limitations must be overcome to enable cord blood stem cell transplants to be widely used. On another front, scientists are studying whether cord blood stem cells could directly differentiate into specialized cells known as dendritic cells, and trigger T cells in the immune system into attacking solid tumors.
Before novel and effective therapies targeted at cancer stem cells can be developed, several questions need to be answered regarding their role in the treatment of solid tumors. Researchers are also trying to better understand the properties and specificity of stem cells. They are still investigating which type of molecules trigger the proliferation of cancer stem cells and which ones reduce it. These questions are currently being investigated by scientists whose objective is to define and implement strategies aimed at efficiently targeting and eradicating cancer stem cells.
Coast-to-coast and all over the United States, clinical research and studies into the treatment of solid tumors are being conducted that hold significant promise for success. A listing of solid tumors medical research trials actively recruiting patient volunteers can be found at https://www.centerwatch.com/clinical-trials/listings/condition/424/solid-tumors.
Latest News: NCI Implements the National Clinical Trials Network
A recently written article discussed the latest initiative of the National Cancer Institute (NCI), which is currently working to launch a clinical trials research network to improve treatment for the million Americans diagnosed with cancer each year. The new initiative hopes to facilitate the implementation of cancer clinical trials to increase efficiency, and to set up a research system that would count more than 3,000 clinical trials sites. Grants to fund the program are expected to “be awarded early in the spring of 2014.”
Morenike Trenou
Independent Scholar
See Also: Adult Stem Cells: Overview; Cancer Stem Cells: Overview; Cord Blood Stem Cells; Hematopoietic Transplantation: Cancer; iPS, Methods to Produce.
Further Readings
Azad, N., et al. “The Future of Epigenetic Therapy in Solid Tumours—Lessons From the Past.” Nature Reviews Clinical Oncology (May 2013).
Bishop, M. R., et al. “NCI 1st International Workshop on the Biology, Prevention, and Treatment of Relapse After Allogeneic Hematopoietic Stem Cell Transplantation: Summary and Recommendations From the Organizing Committee.” Biology of Blood Marrow Transplantation, v.17/4 (2011).
Daley, G. Q. “The Promise and Perils of Stem Cell Therapeutics.” Cell Stem Cell, v.10/6 (2012).
Fang, D. D., D. Wen, and Y. Xu. “Identification of Cancer Stem Cells Provides Novel Tumor Models for Drug Discovery.” Frontiers in Medicine, v.6/2 (2012).
Gluckman, E., et al. “Milestones in Umbilical Cord Blood Transplantation.” British Journal of Haematology, v.154 (2011).
Moore, A. S., et al. “Haemopoietic Stem Cell Transplantation for Children in Australia and New Zealand, 1998–2006: A Report on Behalf of the Australasian Bone Marrow Transplant Recipient Registry and the Australian and New Zealand Children’s Haematology Oncology Group.” Medical Journal of Australia, v.190/3 (2009).
Pelosi, E., G. Castelli, and U. Testa. “Human Umbilical Cord Is a Unique and Safe Source of Various Types of Stem Cells Suitable for Treatment of Haematological Diseases for Regenerative Medicine.” Blood Cells, Molecules, and Diseases, v.49 (2012).
Sampieri, K. and R. Fodde. “Cancer Stem Cells and Metastasis.” Seminars in Cancer Biology, v.22 (2012).
Van Bekkum, D. W. and H. M. M. Mikkers. “Prospects and Challenges of Induced Pluripotent Stem Cells as a Source of Hematopoietic Stem Cells.” Annals of the New York Academy of Sciences, v.1266 (2012).
