Author: Ramisetty, Sravani ; Singhal, Sharad S ; Raghu Subbalakshmi, Ayalur ; Mohanty, Atish ; Kulkarni, Prakash ; Salgia, Ravi ; Pareek, Siddhika ; Garg, Pankaj ; Krishna, Madhu ; Horne, David

Gynecological cancers, including ovarian, cervical, endometrial, and vulvar cancers, present significant challenges in diagnosis and treatment globally. The tumor microenvironment (TME) plays a pivotal role in cancer progression and therapy response, necessitating a deeper understanding of its composition and dynamics. This review offers a comprehensive overview of the gynecological cancer tumor microenvironment, emphasizing its cellular complexity and therapeutic potential. The diverse cellular components of the TME, including cancer cells, immune cells, stromal cells, and extracellular matrix elements, are explored, elucidating their interplay in shaping tumor behavior and treatment outcomes. Across various stages of cancer progression, the TME exerts profound effects on tumor heterogeneity, immune modulation, angiogenesis, and metabolic reprogramming. The urgency for novel therapeutic strategies is underscored by understanding immune evasion mechanisms within the TME. Emerging approaches such as immunotherapy, stromal-targeting therapies, anti-angiogenic agents, and metabolic inhibitors are discussed, offering promising avenues for improving patient outcomes. Interdisciplinary collaborations and translational research are emphasized, aiming to advance precision oncology and enhance therapeutic efficacy in gynecological cancers.

30 Sep 2024·BMB Reports

Metabolic reprogramming of the tumor microenvironment to enhance immunotherapy

Review

Author: Lim, Seon Ah

Immunotherapy represents a promising treatment strategy for targeting various tumor types. However, the overall response rate is low due to the tumor microenvironment (TME). In the TME, numerous distinct factors actively induce immunosuppression, restricting the efficacy of anticancer immune reactions. Recently, metabolic reprogramming of tumors has been recognized for its role in modulating the tumor microenvironment to enhance immune cell responses in the TME. Furthermore, recent elucidations underscore the critical role of metabolic limitations imposed by the tumor microenvironment on the effectiveness of antitumor immune cells, guiding the development of novel immunotherapeutic approaches. Hence, achieving a comprehensive understanding of the metabolic requirements of both cancer and immune cells within the TME is pivotal. This insight not only aids in acknowledging the current limitations of clinical practices but also significantly shapes the trajectory of future research endeavors in the domain of cancer immunotherapy. In addition, therapeutic interventions targeting metabolic limitations have exhibited promising potential as combinatory treatments across diverse cancer types. In this review, we first discuss the metabolic barriers in the TME. Second, we explore how the immune response is regulated by metabolites. Finally, we will review the current strategy for targeting metabolism to not simply inhibit tumor growth but also enhance antitumor immune responses. Thus, we could suggest potent combination therapy for improving immunotherapy with metabolic inhibitors. [BMB Reports 2024; 57(9): 388-399].

30 Jun 2024·Endocrinology and Metabolism

Metabolic Reprogramming in Thyroid Cancer

Review

Author: Kang, Yea Eun ; Lim, Joung Youl ; Ju, Sang-Hyeon ; Song, Minchul ; Shong, Minho ; Yi, Hyon-Seung

Thyroid cancer is a common endocrine malignancy with increasing incidence globally. Although most cases can be treated effectively, some cases are more aggressive and have a higher risk of mortality. Inhibiting RET and BRAF kinases has emerged as a potential therapeutic strategy for the treatment of thyroid cancer, particularly in cases of advanced or aggressive disease. However, the development of resistance mechanisms may limit the efficacy of these kinase inhibitors. Therefore, developing precise strategies to target thyroid cancer cell metabolism and overcome resistance is a critical area of research for advancing thyroid cancer treatment. In the field of cancer therapeutics, researchers have explored combinatorial strategies involving dual metabolic inhibition and metabolic inhibitors in combination with targeted therapy, chemotherapy, and immunotherapy to overcome the challenge of metabolic plasticity. This review highlights the need for new therapeutic approaches for thyroid cancer and discusses promising metabolic inhibitors targeting thyroid cancer. It also discusses the challenges posed by metabolic plasticity in the development of effective strategies for targeting cancer cell metabolism and explores the potential advantages of combined metabolic targeting.

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Indication	Highest Phase	Country/Location	Organization	Date
Metabolic Diseases	Preclinical	AU	Protagonist Therapeutics, Inc.	13 May 2024

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