Neoadjuvant systemic therapy for regionally advanced melanoma

Jakub, James W.; Racz, Jennifer M.; Hieken, Tina J.; Gonzalez, Alexandra B.; Kottschade, Lisa A.; Markovic, Svetomir N.; Yan, Yiyi; Block, Matthew S.

doi:10.1002/jso.24939

Cited by 16 publications

(9 citation statements)

References 17 publications

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“…Similar to neoadjuvant or window-of-opportunity trials in early-stage disease ( 66 , 67 ), IDO inhibitors are under evaluation in several diseases to primarily determine the pathologic effect in the tumor by collecting pre- and post-treatment tissue materials ( 68 , 69 ). Future studies integrating peptide vaccine, anti-angiogenesis agents with IDO1 inhibitors are also of interest in view of its potential synergistic pathways ( 8 ).…”

Section: Results In Clinical Investigationmentioning

confidence: 99%

Updates in the Clinical Development of Epacadostat and Other Indoleamine 2,3-Dioxygenase 1 Inhibitors (IDO1) for Human Cancers

2018

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Recent application of immunotherapy in clinical oncology revolutionized our management of advanced human cancers. Check point inhibitors targeting CTLA4 and PD-1/PD-L1 axis are immunotherapeutic agents currently available to treat a variety of cancers. However, a novel therapeutic approach is needed to further improve patient outcome with these agents. Indoleamine 2,3-dioxygenase 1 (IDO1) is a rate-limiting enzyme in the metabolism of essential amino acid tryptophan in the peripheral tissue. IDO1 is overexpressed in human cancer cells and suppresses effector T cell function and promotes regulatory T cells (Tregs). Overexpression of IDO1 is associated with poor patient survival in several types of human cancer. These findings indicate that IDO1 is a promising target that can improve the treatment outcome in the field of Immuno-oncology. Several orally available IDO1 inhibitors including Epacadostat have entered human clinical trials over the last few years without a major safety concern. Although there is no objective response in single-agent trials, combination regimens with PD-1 inhibitors appear to exceed the activity of PD-1 inhibitors alone. Recent phase III ECHO 301 trial testing the combination of Epacadostat with Pembrolizumab in melanoma did not show superior outcome compared to Pembrolizumab alone. This lead to halting of other phase III trials using IDO1 inhibitors. In this minireview, we will discuss the recent clinical development of Epacadostat and other IDO1 inhibitors.

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Section: Results In Clinical Investigationmentioning

confidence: 99%

Updates in the Clinical Development of Epacadostat and Other Indoleamine 2,3-Dioxygenase 1 Inhibitors (IDO1) for Human Cancers

2018

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“…There are several studies examining the role of neoadjuvant therapy in the setting of technically resectable disease that has shown some promising results that may change the paradigm for some patients . An entire separate review of the neoadjuvant approach appears in this Seminar by Michael Lowe and colleagues.…”

Section: Future Directions and Conclusionmentioning

confidence: 99%

Updates in adjuvant systemic therapy for melanoma

Kwak

Farrow

Salama

et al. 2018

Journal of Surgical Oncology

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There has been a rapid increase in adjuvant therapies approved for treatment following surgical resection of stage III/IV melanoma. We review current indications for adjuvant therapy, which currently includes a heterogenous group of Stage III and IV melanoma patients. We describe several pivotal clinical trials of systemic immune therapies, targeted immune therapies, and adjuvant vaccine strategies. Finally, we discuss the evidence for selecting the most appropriate treatment regimen(s) for the individual patient.

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“…About 75% of deaths in skin cancer are caused by melanoma which had become one of the most difficult human cancers to cure. Once it has spread metastasized, physical therapy is difficult to work and the 5 years survival rate will drop to 20% from 99% [ 2 – 5 ]. Thus, it is urgently required to explore the new prognostic pathways and signatures of melanoma to improve prognosis and guide more effective treatment.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive analysis of cancer hallmarks in cutaneous melanoma and identification of a novel unfolded protein response as a prognostic signature

Wan¹,

Jin²,

Wang³

2020

aging

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Molecular pathways regulating the initiation and development of melanoma are potential therapeutic targets for this aggressive skin cancer. Therefore, transcriptome profiles of cutaneous melanoma were obtained from a public database and used to systematically evaluate cancer hallmark pathways enriched in melanoma. Finally, the unfolded protein response pathway was screened out, and the unfolded protein response-related genes were used to develop a robust biomarker that can predict the prognosis of melanoma, especially for younger, metastatic and high Clark level patients. This biomarker was further validated in two other independent datasets. In addition, melanoma patients were divided into high- and low-risk subgroups by applying a risk score system. The high-risk group exhibited higher immune infiltration and higher expression of N6-methyladenosine RNA methylation regulators, and had significantly shorter survival times than the low-risk subgroup. Gene Set Enrichment Analysis revealed that, among the enriched genes, gene sets involved in immune response and the extracellular matrix receptor interaction were significantly activated in the high-risk group. Our findings thus provide a new clinical application for prognostic prediction as well as potential targets for treatment of melanoma.

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Neoadjuvant systemic therapy for regionally advanced melanoma

Cited by 16 publications

References 17 publications

Updates in the Clinical Development of Epacadostat and Other Indoleamine 2,3-Dioxygenase 1 Inhibitors (IDO1) for Human Cancers

Updates in the Clinical Development of Epacadostat and Other Indoleamine 2,3-Dioxygenase 1 Inhibitors (IDO1) for Human Cancers

Updates in adjuvant systemic therapy for melanoma

Comprehensive analysis of cancer hallmarks in cutaneous melanoma and identification of a novel unfolded protein response as a prognostic signature

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