HIPOXIA-INDUCIBLE FACTOR 1 (HIF-1) DAN ANGIOGENESIS TUMOR: MEKANISME, IMPLIKASI KLINIS, DAN POTENSI TERAPI
HIPOXIA-INDUCIBLE FACTOR 1 (HIF-1) AND TUMOR ANGIOGENESIS: MECHANISMS, CLINICAL IMPLICATIONS, AND THERAPEUTIC POTENTIAL
Abstract
Hypoxia plays a crucial role in tumor development and progression by inducing angiogenesis. One of the key mediators in the hypoxic response is Hypoxia-Inducible Factor-1 (HIF-1), which regulates the expression of pro-angiogenic genes such as vascular endothelial growth factor (VEGF). HIF-1 activation, whether through hypoxic conditions or genetic mutations, contributes to the formation of new blood vessels that support tumor growth and metastasis. This article is a narrative review aimed at summarizing the molecular mechanisms of HIF-1 in tumor angiogenesis and exploring its potential as a target for cancer therapy. The discussion includes HIF-1 regulation under normoxic and hypoxic conditions, its impact on the structure of tumor vasculature, and the development of therapies targeting the HIF-1 pathway, such as HIF-1α inhibitors, dimerization blockers, and degradation-inducing agents. By understanding the central role of HIF-1 in angiogenesis and tumor progression, this article aims to contribute a scientific foundation for the development of anti-angiogenic therapies and future research in the field of molecular oncology.
Abstrak
Hipoksia merupakan kondisi yang berperan penting dalam perkembangan dan progresi tumor melalui induksi angiogenesis. Salah satu mediator utama dalam respons hipoksia adalah Hypoxia-Inducible Factor-1 (HIF-1), yang berperan sebagai regulator utama homeostasis oksigen. HIF-1 mengatur ekspresi berbagai gen yang terlibat dalam angiogenesis, termasuk vascular endothelial growth factor (VEGF), angiopoietin, dan faktor pertumbuhan lainnya. Dalam kondisi hipoksia, HIF-1α tidak mengalami degradasi, sehingga terjadi peningkatan ekspresi VEGF yang memicu pembentukan pembuluh darah baru guna memenuhi kebutuhan oksigen sel tumor. Selain itu, mutasi pada onkogen dan tumor suppressor genes dapat menyebabkan aktivasi HIF-1 yang tidak tergantung pada hipoksia, sehingga semakin meningkatkan angiogenesis tumor. Pemahaman lebih lanjut tentang peran HIF-1 dalam angiogenesis telah membuka peluang untuk pengembangan terapi target kanker yang menghambat jalur HIF-1. Terapi ini mencakup inhibisi ekspresi HIF-1α, pencegahan dimerisasi dengan HIF-1β, serta penghambatan interaksi dengan DNA. Dengan demikian, modulasi jalur HIF-1 dapat menjadi pendekatan yang menjanjikan dalam terapi kanker berbasis anti-angiogenesis.
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