推进软骨肉瘤的全身治疗：新视野。

IF 3.2 Q2 ONCOLOGY

Oncology and Therapy Pub Date : 2024-12-09 DOI:10.1007/s40487-024-00317-z

Ka Hou C Li, Ashish Gulia, Florence Duffaud, Robin L Jones

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引用次数: 0

摘要

晚期和转移性软骨肉瘤是一种对常规治疗反应有限的恶性肿瘤，其全身治疗前景一直是众所周知的挑战。虽然标准化疗提供的益处微乎其微，但某些亚型，如间充质和去分化软骨肉瘤，已经对最初为其他肉瘤开发的全身治疗显示出一些反应。研究策略集中在分子靶点，包括异柠檬酸脱氢酶基因（IDH）突变、信号通路，如刺猬和死亡受体5 （DR5）和免疫调节。IDH突变，特别是在常规和去分化软骨肉瘤中发现，促使对IDH抑制剂的评估，尽管在软骨肉瘤中的数据有限，但在临床前和早期临床试验中显示出有希望的疗效。此外，与软骨肉瘤进展有关的hedgehog途径已被抑制剂靶向，尽管临床翻译显示出不同的结果。免疫疗法，包括程序性细胞死亡1 （PD-1）检查点抑制剂和嵌合抗原受体t （CAR-T）细胞，也正在研究中，但由于免疫抑制肿瘤微环境面临挑战。在新方法中，DR5激动剂如INBRX-109已显示出单药疗效，毒性最小，为联合治疗提供了改善预后的可能性。鉴于软骨肉瘤的异质性和治疗耐药性，我们强调需要多组学和基因谱来指导针对多种致癌途径的个性化联合治疗。多靶点方法的整合可以提高疗效，解决肿瘤异质性，克服耐药性，为这种具有挑战性的癌症的全身治疗提供了一个有希望的方向。IDH抑制剂、免疫疗法和DR5激动剂联合治疗方案的研究有望改变晚期软骨肉瘤的治疗。

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Advancing Systemic Therapy in Chondrosarcoma: New Horizons.

The systemic treatment landscape for advanced and metastatic chondrosarcoma, a malignancy with limited responsiveness to conventional therapies, has always been notoriously challenging. While standard chemotherapy offers minimal benefits, certain subtypes, such as mesenchymal and dedifferentiated chondrosarcomas, have shown some response to systemic therapies initially developed for other sarcomas. Investigational strategies are focusing on molecular targets, including mutations in the isocitrate dehydrogenase gene (IDH), signaling pathways, such as hedgehog and death receptor 5 (DR5) and immune modulation. IDH mutations, notably found in conventional and dedifferentiated chondrosarcomas, have prompted the evaluation of IDH inhibitors, which have demonstrated promising efficacy in preclinical and early clinical trials, despite limited data in chondrosarcoma. Additionally, the hedgehog pathway, implicated in chondrosarcoma progression, has been targeted with inhibitors, although clinical translation has shown mixed results. Immunotherapy, including programmed cell death 1 (PD-1) checkpoint inhibitors and chimeric antigen receptor-T (CAR-T) cells, is also being investigated but faces challenges due to the immunosuppressive tumour microenvironment. Among new approaches, DR5 agonists such as INBRX-109 have shown single-agent efficacy, with minimal toxicity, opening possibilities for use in combination therapies to improve outcomes. Given the heterogenous and treatment-resistant nature of chondrosarcoma, we highlight the need for multi-omics and genetic profiling to guide personalized, combination therapies that target multiple carcinogenic pathways. The integration of multi-targeted approaches could enhance efficacy, address tumour heterogeneity, and overcome resistance, presenting a hopeful direction for systemic therapy in this challenging cancer. The investigation of combination regimens with IDH inhibitors, immunotherapy and DR5 agonists hold promise for transforming the management of advanced chondrosarcoma.

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来源期刊

Oncology and Therapy ONCOLOGY-

CiteScore

3.40

自引率

0.00%

发文量

审稿时长

6 weeks

期刊介绍： Now indexed in PubMed Aims and Scope Oncology and Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality pre-clinical, clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all therapeutic areas. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Oncology and Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research. Rapid Publication The journal’s rapid publication timelines aim for a peer review decision within 2 weeks of submission. If an article is accepted it will be published online 3-4 weeks from acceptance. These rapid timelines are achieved through the combination of a dedicated in-house editorial team, who closely manage article workflow, and an extensive Editorial and Advisory Board who assist with rapid peer review. This allows the journal to support the rapid dissemination of research, whilst still providing robust peer review. Combined with the journal’s open access model this allows for the rapid and efficient communication of the latest research and reviews, allowing the advancement of clinical therapies. Personal Service The journal’s dedicated in-house editorial team offer a personal “concierge service” meaning that authors will always have a personal point of contact able to update them on the status of their manuscript. The editorial team check all manuscripts to ensure that articles conform to the most recent COPE, GPP and ICMJE publishing guidelines. This supports the publication of ethically sound and transparent research. We also encourage pre-submission enquiries and are always happy to provide a confidential assessment of manuscripts. Digital features and plain language summaries Oncology and Therapy offers a range of additional features designed to increase the visibility, readership and educational value of the journal’s content. 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All suitable submissions are then subject to a comprehensive single-blind peer review. Reviewers are selected based on their relevant expertise and publication history in the subject area. The journal has an extensive pool of editorial and advisory board members who have been selected to assist with peer review based on the afore-mentioned criteria. At least two extensive reviews are required to make the editorial decision, with the exception of some article types such as Commentaries, Editorials and Letters which are generally reviewed by one member of the Editorial Board. Where reviewer recommendations are conflicted, the editorial board will be contacted for further advice and a presiding decision. Manuscripts are then either accepted, rejected or authors are required to make major or minor revisions (both reviewer comments and editorial comments may need to be addressed). 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