Chaudhry Gul-E-Saba, Akim Abdah, Naveed Zafar Muhammad, Safdar Naila, Sung Yeong Yik, Muhammad Tengku Sifzizul Tengku
Institute of Marine Biotechnology, Universiti Malaysia Terengganu, 21030 Kuala Terengganu, Malaysia.
Department of Biomedical Sciences, Universiti Putra Malaysia, Seri Kembangan, Selangor, Malaysia.
Adv Pharm Bull. 2021 May;11(3):426-438. doi: 10.34172/apb.2021.050. Epub 2020 Jul 15.
Cancer is a complex mechanism involving a series of cellular events. The glycoproteins such as hyaluronan (HA) are a significant element of extracellular matrix (ECM), involve in the onset of cancer developmental process. The pivotal roles of HA in cancer progression depend on dysregulated expression in various cancer. HA, also gain attention due to consideration as a primary ligand of CD44 receptor. The CD44, complex transmembrane receptor protein, due to alternative splicing in the transcription process, various CD44 isoforms predominantly exist. The overexpression of distinct CD44 isoforms (CD44v) standard (CD44s) depends on the tumour type and stage. The receptor proteins, CD44 engage in a variety of biological processes, including cell growth, apoptosis, migration, and angiogenesis. HA-CD44 interaction trigger survival pathways that result in cell proliferation, invasion ultimately complex metastasis. The interaction and binding of ligand-receptor HA-CD44 regulate the downstream cytoskeleton pathways involve in cell survival or cell death. Thus, targeting HA, CD44 (variant and standard) isoform, and HA-CD44 binding consider as an attractive and useful approach towards cancer therapeutics. The use of various inhibitors of HA, hyaluronidases (HYALs), and utilizing targeted Nano-delivery of anticancer agents and antibodies against CD44, peptides gives promising results and . However, they are in clinical trials with favourable and unfavourable outcomes, which reflects the need for various modifications in targeting agents and a better understanding of potential targets in tumour progression pathways.
癌症是一种涉及一系列细胞事件的复杂机制。诸如透明质酸（HA）等糖蛋白是细胞外基质（ECM）的重要组成部分，参与癌症发展过程的起始。HA在癌症进展中的关键作用取决于其在各种癌症中的表达失调。由于HA被认为是CD44受体的主要配体，它也受到了关注。CD44是一种复杂的跨膜受体蛋白，由于转录过程中的可变剪接，主要存在多种CD44异构体。不同CD44异构体（CD44v）与标准型（CD44s）的过表达取决于肿瘤类型和阶段。受体蛋白CD44参与多种生物学过程，包括细胞生长、凋亡、迁移和血管生成。HA-CD44相互作用触发存活途径，最终导致细胞增殖、侵袭和复杂的转移。配体-受体HA-CD44的相互作用和结合调节涉及细胞存活或死亡的下游细胞骨架途径。因此，靶向HA、CD44（变体和标准型）异构体以及HA-CD44结合被认为是一种有吸引力且有用的癌症治疗方法。使用各种HA抑制剂、透明质酸酶（HYALs），以及利用靶向纳米递送抗癌药物和针对CD44的抗体、肽，都取得了有前景的结果。然而，它们正处于临床试验阶段，结果有好有坏，这反映出需要对靶向药物进行各种改进，并更好地了解肿瘤进展途径中的潜在靶点。
