Targeting the undruggable: exploiting neomorphic features of fusion oncoproteins in childhood sarcomas for innovative therapies

AbstractWhile sarcomas account for approximately 1% of malignant tumors of adults, they are particularly more common in children and adolescents affected by cancer. In contrast to malignancies that occur in later stages of life, childhood tumors, including sarcoma, are characterized by a striking paucity of somatic mutations. However, entity-defining fusion oncogenes acting as the main oncogenic driver mutations are frequently found in pediatric bone and soft-tissue sarcomas such as Ewing sarcoma (EWSR1-FLI1), alveolar rhabdomyosarcoma (PAX3/7-FOXO1), and synovial sarcoma (SS18-SSX1/2/4). Since strong oncogene-dependency has been demonstrated in these entities, direct pharmacological targeting of these fusion oncogenes has been excessively attempted, thus far, with limited success. Despite apparent challenges, our increasing understanding of the neomorphic features of these fusion oncogenes in conjunction with rapid technological advances will likely enable the development of new strategies to therapeutically exploit these neomorphic features and to ultimately turn the “undruggable” into first-line target structures. In this review, we provide a broad overview of the current literature on targeting neomorphic features of fusion oncogenes found in Ewing sarcoma, alveolar rhabdomyosarcoma, and synovial sarcoma, and give a perspective for future developments.Graphical abstractScheme depicting the different targeting strategies of fusion oncogenes in pediatric fusion-...
Source: Cancer and Metastasis Reviews - Category: Cancer & Oncology Source Type: research

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Thousands of men across the world have participated in randomized clinical trials testing the role of hormone therapy in the curative treatment of localized, high-risk prostate cancer. Over several decades, we have established that long-term hormone therapy improves survival, even in the setting of dose-escalated external beam radiation therapy (EBRT).1 Recently reported clinical trials suggest that for some men 18 months of hormone therapy may be a suitable duration that balances treatment efficacy with quality-of-life preservation.
Source: International Journal of Radiation Oncology * Biology * Physics - Category: Radiology Authors: Tags: Editorial Source Type: research
We welcome 3 new associate editors: Drs Christopher Anker (University of Vermont Larner College of Medicine), Michael Buckstein (Icahn School of Medicine at Mount Sinai), and Jordan Kharofa (University of Cincinnati College of Medicine), whom were selected for their timely and thoughtful critiques as Red Journal reviewers. Although all 3 reviewers are experts in gastrointestinal (GI) radiation oncology, Dr Anker provides expertise in esophageal and rectal cancers, Dr Buckstein in liver cancers and translational science, and Dr Kharofa in pancreatic and anal cancers.
Source: International Journal of Radiation Oncology * Biology * Physics - Category: Radiology Authors: Tags: Feature Source Type: research
To clarify the relative effects of duration of androgen suppression (AS) and radiation dose escalation (RDE) on distant progression (DP) in men with locally advanced prostate cancer.
Source: International Journal of Radiation Oncology * Biology * Physics - Category: Radiology Authors: Tags: Clinical Investigation Source Type: research
We thank the authors1 for their letter highlighting the critical issues facing the feasibility and efficacy of stereotactic ablative radiation (SAbR) as a boost for patients with cervical cancer unable to receive standard brachytherapy.
Source: International Journal of Radiation Oncology * Biology * Physics - Category: Radiology Authors: Tags: Comment Source Type: research
We applaud the University of Texas Southwestern Department of Radiation Oncology for conducting “A phase II trial of stereotactic ablative radiotherapy as a boost for locally advanced cervical cancer,” a necessary prospective study on definitive dose delivery for patients unable to undergo brachytherapy.1 The involved trialists were undoubtedly deliberate and meticulous in its design and e xecution, akin to their groundbreaking work with lung stereotactic body radiation therapy (SBRT). Although these results unfortunately showed high rates of rectal toxicity, the data does not indicate a failure of SBRT, but ra...
Source: International Journal of Radiation Oncology * Biology * Physics - Category: Radiology Authors: Tags: Comment Source Type: research
A 58-year-old female presents with a 1-year history of hematochezia, 20-pound weight loss, and increased straining with bowel movements. She denies increased bowel frequency or change in stool caliber. Her medical history is notable for irritable bowel syndrome, but otherwise unremarkable. She has no family history of malignancy and does not take any prescribed medications or supplements. She denies abdominal pain, bone pain, or any symptoms concerning for metastatic disease. Her initial physical examination was notable for an Eastern Cooperative Oncology Group performance status of 0, and presence on digital rectal examin...
Source: International Journal of Radiation Oncology * Biology * Physics - Category: Radiology Authors: Tags: Gray Zone Source Type: research
In Africa, there were over 846,000 new cancer cases and 591,000 deaths in 2012. These figures are projected to rise to 1.27 million cases and 0.97 million deaths annually by 20301 as a result of population growth and aging alone.
Source: International Journal of Radiation Oncology * Biology * Physics - Category: Radiology Authors: Tags: Feature Source Type: research
Introduction: Bioelectrical impedance vector analysis (BIVA) is a non-invasive method for measuring body composition. The “InForma” trial has been designed to measure improvement of adherence to a healthy diet and/or to increase physical activity in order to promote weight loss in overweight or obese breast cancer survivors. Breast cancer survivors frequently face progressive weight gain and diminution of physical activity.
Source: Nutrition, Metabolism, and Cardiovascular Diseases : NMCD - Category: Nutrition Authors: Source Type: research
Introduction: Breast cancer (BC) is the most common cancer in women and the 5-year survival rate is 82% in Europe. Obesity, metabolic syndrome and diabetes are associated with an increased risk of BC and BC recurrence. Physical activity (PA), Mediterranean diet (MeD) and low glycemic index (GI) or high fiber diets, however, are protective.
Source: Nutrition, Metabolism, and Cardiovascular Diseases : NMCD - Category: Nutrition Authors: Source Type: research
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Source: MDDI - Category: Medical Devices Authors: Tags: Business Source Type: news
More News: Bone Cancers | Cancer | Cancer & Oncology | Cancer in Adolescents | Child Development | Childhood Cancer | Children | Ewing's Sarcoma | Pediatrics | Rhabdomyosarcoma | Sarcomas | Soft Tissue Sarcoma | Synovial Sarcoma