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On the way to find a medication for any type of sarcoma
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After years of stagnation, the field of personalized medicine makes a huge step forward in the field of sarcoma therapy, and will offer the patients an optimal treatment for their disease.
X-ray and MRI imaging of knee sarcoma. Cancer is a family of diseases, in which each has its own course and its own treatment.
Among hundreds of types and thousands of subtypes of cancerous tumors, there is also a diverse but less known family of tumors: the sarcomas. These are tumors develop in patients of any age and are located in skeletal bones, muscles and other tissues that support or connect the bones. It is not another type of cancer, but a group of tumors that are problematic, since each sarcoma is a cancer in itself, which has a typical disease course and typical sensitivity to drugs and radiation therapy, and which requires unique diagnostic methods. Despite the fact that there are about 70 different types of sarcomas, these tumors are still very rare. Until the last few years, the treatment of metastatic sarcomas, except for individual tumor types (originating in bone, cartilage or gastrointestinal tract), was the same and included chemotherapy based on combination of two drugs: Doxorubicin and Ifosfamide. After many years in which treatment of sarcomas was not developing and relied mainly on chemotherapy, a conceptual change seems to emerge in the treatment. Due to the in-depth understanding of biological and genetic processes in oncology in general and sarcoma in particular, today treatments rely on careful identification of the type of sarcoma of the 70 known types and adaptation of treatment and access. In the last decade, major changes have occurred in the field of oncology. Two breakthroughs led the field to new areas: Immunotherapy - a treatment that stimulates the patient`s immune system to fight tumor, and precise targeted therapies (biological preparations) that selectively inhibit protein activity in the tumor without affecting the healthy tissue. These treatments achieve an impressive improvement in patients` life expectancy, and have a completely different profile of side effects than chemotherapy. In the annual meeting of the American Society of Clinical Oncology (ASCO) held last June in Chicago, an international conference attended by about 40,000 oncologists from around the world, there was a special session entitled “New approaches to treatment of sarcomas: The development of precise and personalized medicine.” The approach of treating each sarcoma type separately was one of the main motives in the various lectures that focused on sarcoma cases, in which immunotherapy, biological therapy, and chemotherapy provided good outcomes. Recent studies presented at the conference already refer to various types of sarcoma tumors as different diseases and not as one general disease, as has been the case until now. For example, two different studies tested two drugs for dedifferentiated liposarcoma - tumors that originate in fatty tissue. Studies have shown that two biological drugs allow pausing chemotherapy. One of them is the biological drug Palbociclib, which is currently approved for the treatment of metastatic breast cancer, and provides stabilization in 60% of the patients for three months at least, during which they do receive chemotherapy. The second drug is Selinexor, which was found in a second phase study in the United States to induce a disease remission of 5.6 months versus 1.8 months in the placebo group. In GIST sarcoma, which develops in the digestive tract, the biological treatment Imatinib (known as Glivec) has changed the fate of patients with unresectable tumors. From a chemotherapy-resistant disease that was omitted from clinical trials that have examined chemotherapy since year 2000, it has become a controlled disease with excellent and long-term treatment responses. Two new drugs are currently being developed for patients with a rare GIST which is resistant to Imatinib. Another type of sarcoma develops in a single joint and causes severe damage without metastasis (Tenosynovial Giant Cell Tumor). The tumor is characterized by an enormous number of inflammatory cells and relatively few tumor cells. Two biological treatments that are currently tested in clinical trials prevent the inflammatory cells from entering the tumor cell environment causing the disease. The new treatments produce a complete regression of the tumor in about 10% of the patients, and the rest will enjoy a reduction or stabilization of the size. Another example is an innovative treatment for angiosarcoma tumors, which are multivascular tumors that spontaneously appear or rarely develop in body parts treated with radiotherapy many years earlier. A new treatment that includes an antibody called TRC105 to a protein associated with vascular proliferation and development. The treatment has shown remarkable efficacy, especially in combination with Pazopanib, a biologic drug approved for the treatment of sarcomas from a soft tissue source. The disease disappeared completely in two of the 18 patients treated with this drug combination, and the median progression-free survival (the time since diagnosis, or the last treatment until half of the patients are alive) was unchanged for 7.8 months. The list is long and includes more genetic features and new experimental treatments of various sarcoma tumors. It is important to emphasize that not all sarcomas respond to immunotherapy treatments. Experience has shown that there are characteristics that predict better chances of success, such as multiple mutations and high expression of genes associated with immune response. In fact, most types of sarcoma do not have the characteristics known to doctors as making tumors respond well to immunotherapy, with the exception of undifferentiated pleomorphic liposarcoma (UPS) Its treatment is still experimental, but this sarcoma has the highest potential for the success of immunotherapy. In order to increase the response rates of the other sarcomas, current studies use combined strategies that include different treatment types. This can be chemotherapy combined with immunotherapy drugs, or radiotherapy with a direct injection of the drug to the tumor. The purpose of these combinations is double: To stimulate an immune response by intracellular proteins first exposed to immune cells when the cancerous cell dies and its content goes out, and suppress the activity of immune cells that inhibit the immune response. At this time point, oncology brings good news to some patients with sarcoma. The understanding of the biological mechanism and the genetic profile of tumors allows personalized medicine that is still in its infancy, but is already showing positive outcomes and provides optimism for the future to come. The new treatments are a good addition to the therapeutic toolbox, and doctors use them in disease management concomitantly or instead of current treatments.
Dr. Daniella Katz - Director of the Breast Cancer and Sarcoma Service at the Oncology Institute at the Shamir Medical Center - Assaf Harofeh. Guided and lectured at a session dealing with sarcoma tumors at the ASCO conference
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