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There are a number of articles on immunotherapy and related clinical trials cited in the Q and A on Immunotherapy column in this issue of ESUN. There are also some additional immunotherapy references in the Clinical Trial News column. We complete this focus on immunotherapy by listing several additional immunotherapy resources.
Among the articles in the February 2004 issue of Current Opinion in Molecular Therapeutics (Vol. 6, Is. 1) are Cancer vaccines: a critical review on clinical impact, by R. J. Bitton, (pp. 17-26) and Therapeutic cancer vaccines, by B. Acres, S. Paul, H. Haegel-Kronenberger, B. Calmels, and P. Squiban, (pp 40-47).
The abstract of the Bitton paper states, in part, “The aim of this article is to review the most commonly used cancer vaccine strategies and to evaluate the evidence supporting their efficacy. This is not as easy at it may sound, as each research group involved in cancer vaccine development uses different technologies, targets different antigens, combines different carriers and adjuvants to obtain an immune response, and immunizes patients with different administration schedules. The final picture is somewhat confusing, and comparison of different vaccine strategies is almost impossible. Most of the vaccines are still experimental, far from being approved by regulatory authorities, and their clinical utility is almost negligible.”
The abstract of the Acres article states, in part, “Therapeutic vaccination against cancer-associated antigens represents an attractive option for cancer therapy in view of the comparatively low toxicity and, so far, excellent safety profile of this treatment. Nevertheless, it is now recognized that the vaccination strategies used for prophylactic vaccinations against infectious diseases cannot necessarily be used for therapeutic cancer vaccination. Cancer patients are usually immunosuppressed, and most cancer-associated antigens are self antigens. Therefore, various immunostimulation techniques are under investigation in an effort to bolster immune systems and to overcome immune tolerance to self antigens. … Aggressive protocols such as those combining specific stimulation of T-cells and chemotherapy or strategies to block immune regulation are having some success.”
An earlier review paper by Bitton and his colleagues discusses the immunogenicity of tumor cells, the mechanism of immune evasion, various anticancer vaccine approaches, allogeneic or autologous, cellular vaccines, vaccines with specific defined antigens, ganglioside based vaccines, and the clinical development and current status of cancer vaccines (circa 2002). You can download a PDF of this paper by clicking on its title, Cancer vaccines: An update with special focus on ganglioside antigens, by Roberto J. Bitton, Marcelo Guthmann, Mariano Gabri, Ariel Carbero, Daniel Alonso, Leonardo Fainboim and Daniel Gomez, Oncology Reports, 9: 267-276, 2002.
You can access a 2002 CME course on Therapeutic Cancer Vaccines: Targeting the Future of Cancer Treatment from the Medscape website. It is designed for clinical oncologists and research fellows. However, the website also states that, “Others who may benefit include immunologists, oncology nurses, and other health care professionals involved in the research and clinical care of patients with cancer and/or cancer susceptibility.” It further states that “Upon completion of this activity, participants should be able to: (1) Define advantages and drawbacks of current cancer vaccine strategies; (2) Identify potential patient populations appropriate for therapeutic vaccines in various tumor types; and (3) Explore ongoing clinical trials of therapeutic vaccines targeting specific tumor-associated antigens and understand their clinical application and relevancy."
Cryoma Labs, a firm that provides tumor cell and tumor tissue banking (processing and storage) for individuals, has a brief webpage discussing sarcoma vaccines. AVAX Technologies is another company that can bank a patient’s tumor cells/tissues. Tumor banking is not new and has been used for several decades; see, for example the Herbert Irving Comprehensive Cancer Center’s Experimental Molecular Pathology Core Facility. Tissue banking is mentioned numerous times in the National Cancer Institute’s Sarcoma Progress Review Group report, A Roadmap for Sarcoma Research, that is discussed in this issue of ESUN.
Gene Expression Profiling in Soft Tissue Sarcomas The discovery that genetic fingerprinting can differentiate between similar subtypes of soft-tissue sarcomas (STS) that look identical under a microscope may lead to improved diagnosis of these rare cancers and possibly to the development of new, more targeted therapies that attack sarcomas based on their unique genetic differences. In their article, Classification and Subtype Prediction of Adult Soft Tissue Sarcoma by Functional Genomics (American Journal of Pathology, Vol. 163, No. 2, August 2003), Dr. Segal and his co-authors propose that “gene expression profiling in soft tissue sarcoma would identify a genomic based classification scheme that is useful in diagnosis”. As part of their conclusions, they state, “The classification of STS will continue to evolve as additional subtypes of this disease are introduced into the molecular classification scheme. More detailed analysis of the gene expression profiles of each of the more than 50 subtypes of STS will clarify the biological differences within STS and will hopefully propose therapies specific for each subclass of STS, if not therapy specific for an individual patient’s tumor.” They propose “multiple molecular pathways that may become potential targets for therapeutic intervention, and represents one step toward a comprehensive molecular understanding of this rare and heterogeneous group of diseases”.
Genetic Profiling of Leiomyosarcoma Tumors In their article, Tumor Specific Gene Expression Profiles in Human Leiomyosarcoma: An Evaluation of Intratumor Heterogeneity (CANCER April 1, 2002, V. 94, N. 7, pp. 2069-2075), Dr. Shmulevich and his colleagues note that, “Leiomyosarcoma has increased in incidence from 10% to 31% of all sarcomas over the last 10 years. Because of the unpredictable clinical behavior and the lack of objective surrogate markers for its evaluation, progress in the management of these tumors has been minimal”. They show that “the intratumor heterogeneity in leiomyosarcoma is insignificant from the standpoint of genetically profiling these tumors. This observation, in turn, permits one to establish an objective molecular model for leiomyosarcomas regardless of tumor size. They hope to eventually to be able “to identify profiles that are related clinically and, in the process, identify strong feature genes that are of diagnostic or prognostic importance for leiomyosarcomas. In addition, these expression profiles may identify therapeutic targets that are significant in the treatment of soft tissue sarcomas.”
Additional (non-immunotherapy) Research Corner Notes Using post-operative anti-angiogenic therapy in patients with osteosarcoma There is a unique phenomenon in which animals that have large primary tumors may be resistant to the growth of smaller metastatic tumors by systemic angiogenic suppression. This phenomenon is called concomitant tumor resistance, CTR. In their paper, Concomitant tumor resistance in patients with osteosarcoma. A clue to a new therapeutic strategy (J Bone Joint Surg Br. 2004 Jan; 86(1): pp. 143-7) Dr. Kaya and his co-authors report on a study to clinically examine this phenomenon. Their findings suggest that, “the presence of CTR in patients with osteosarcoma for whom post-operative antiangiogenic therapy may be used to prevent the post-operative progression of micro metastases”. Click here to see the Q&A on Angiogenesis that appeared in the first issue of ESUN.
Soft Tissue Sarcomas I would venture to say that many ESUN readers will have read, at one time or another, an article titled “Soft Tissue Sarcomas” in their quest to help them understand sarcomas. Drs. Cormier and Pollock of MD Anderson Cancer Center have recently added a noteworthy, identically named article to the literature. It appears in the March/April issue of “CA: A Cancer Journal for Clinicians”. The article discusses the incidence, epidemiology, genetics, clinical presentation, diagnostic staging, biopsy techniques, staging and prognostic factors, and various types of treatments. It contains a “special situation” section on retroperitoneal, gastrointestinal and recurrent sarcomas and lists over 120 references. Their conclusion states, “Soft tissue sarcomas are a heterogeneous group of rare tumors. The vast majority of the tumors are sporadic. The management of such diverse tumors is complex and depends on the stage, site, and histologic characteristics of the tumor. The most common site of metastasis is the lungs, and metastasis generally occurs within two to three years after the completion of therapy. Progress is, however, being made in our understanding of the molecular characteristics of these tumors. This information should in the near future translate into molecularly based therapies that can be incorporated into standard treatment strategies that together will be of increasing benefit to all patients with soft tissue sarcomas.” A PDF of the complete article can be downloaded by clicking here. It is well worth the read.
Treatment within Specialized Sarcoma Centers Dr. Ray-Coquard et al show that the primary management of adult soft tissue sarcomas (STS) is improved when coordinated by specialized sarcoma centers in their article, Conformity to clinical practice guidelines, multidisciplinary management and outcome of treatment for soft tissue sarcomas (Annals of Oncology 15:307-315, 2004). Their study involved 100 patients with a median age of 58 years (range 18–88 years) and the median tumor size was 9 cm (range 1–26 cm). The most common primary sites were extremities, viscera or trunk and the most frequent sarcomas were leiomyosarcoma (21%) and liposarcoma (12%). This study, compared STS patients treated within and outside the cancer network and retrospectively assessed the conformity of medical practice with evidence-based medicine (EBM) reported under the clinical practice guidelines (CPGs) of the French Federation of Cancer Centers. They conclude that, “Elaboration of treatment strategy within a formal multidisciplinary staff and treatment within a cancer network are both important prognostic factors for optimal clinical care”.
Enalapril and Cardiac Function Decline Doxorubicin, an anthracycline, is often used in sarcoma protocols. The purpose of the study that Dr. Silber and his co-authors reported on in their article, Enalapril to Prevent Cardiac Function Decline in Long-Term Survivors of Pediatric Cancer Exposed to Anthracyclines (Journal of Clinical Oncology, Vol 22, No 5 (March 1), 2004: pp. 820-828) was to, “determine whether an angiotensin-converting enzyme (ACE) inhibitor, enalapril, prevents cardiac function deterioration (defined using maximal cardiac index (MCI) on exercise testing or increase in left ventricular end-systolic wall stress (LVESWS) in long-term survivors of pediatric cancer.” They conclude that, “Enalapril treatment did not influence exercise performance, but did reduce LVESWS in the first year; this reduction was maintained over the study period. Any theoretical benefits of LVESWS reduction in this anthracycline-exposed population must be weighed against potential side effects from ACE inhibitors when making treatment decisions.”
Soft Tissue Tumor Online India This website is due to Dr. Sampurna Roy of West Bengal-Calcutta, India and covers a wide spectrum of topics related to soft tissue tumors. He states, “Soft tissue tumour is a complex subject and reporting a case can sometimes be a difficult and perplexing task. … I hope the information will be useful for diagnostic pathologists, clinicians and trainee pathologists.” A wide range of sarcomas are included; among them are alveolar soft part sarcoma, clear cell sarcoma, epithelioid sarcoma, extraskeletal Ewing's sarcoma/PNET, and synovial sarcoma. The grading of soft tissue sarcomas is also discussed.
V1N2 ESUN Copyright © 2004 Liddy Shriver Sarcoma Initiative.
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