Beta-blokerlerin yeniden konumlandırılması: Meme kanseri uygulamaları

Adrenerjik reseptörlerin yanıtını (aktivasyonunu) engelleyen beta-adrenerjik reseptör antagonistleri, beta-blokerler olarak adlandırılır. Beta-blokerler hipertansiyon, infatil hemanjiyom anormal stres, iskemik kalp yetmezliği gibi kardiyovasküler durumların tedavisi için yaygın olarak kullanılan ilaçları kapsamaktadır. Tümör mikroçevresindeki tümör ve stromal hücrelerin β-AR uyarımı, tümör büyümesini ve metastatik yayılımı teşvik etmekte ve sağkalımı olumsuz etkilemektedir. İlaçları yeniden yapılandırma, yönlendirme, profillendirme veya konumlandırma olarak adlandırılan strateji, klinik kullanımda var olan bir ilacı olduğu gibi ya da yapısal modifikasyona uğratarak yeni bir endikasyona uyarlamak ya da kullanmak olarak tanımlanmaktadır. Artan kanser vakaları nedeniyle kanser tedavisinin maliyeti artmaktadır. Günümüzde bu maliyetin düşürülmesi ve kanser tedavisinin etkinliğinin artırılması amaçlanmaktadır. Beta-blokerlerın, β-AR uyarımı engelleyerek sinyal yolağında bulunan alt efektörlerin aktivasyonunu ve bunlar ile uyarılan diğer yolakları engellediği bilinmektedir. Ek olarak, beta-blokerlerin hücrelerde proliferasyonu engelleyerek apoptozu uyardığı ile ilgili veriler de mevcuttur. Propranololün meme kanseri hastalarında yeniden konumlandırma çalışmaları, umut vadeden verilerin elde edilmesini sağlamıştır. Bu derlemede, yeniden konumlandırılmış ilaçlar, beta-blokerlerin kanser hücreleri üzerindeki etki mekanizmaları ile bu ilaçların meme kanseri tedavisinde kullanımını konu alan çalışmaların değerlendirilemesi yapılmıştır. Beta-blokerler dahil olmak üzere meme kanseri tedavisi için yeniden konumlandırılan ilaçlar ile ilgili klinik öncesi ve klinik çalışmaların arttırılması, kanser tedavi stratejilerinin çeşitlendirilmesi ve maliyetlerin düşürülmesi açısından kritik öneme sahiptir.

Anahtar Kelimeler:

Adrenerjik reseptör, ilaç yeniden konumlandırma, kardiyovasküler ilaçlar, katekolamin, meme kanseri, propranolol

Repurposing of beta-blockers: Applications in breast cancer

Beta-adrenergic receptor (β-AR) antagonists inhibiting receptor activation are called beta-blockers. Beta-blockers are commonly used to treat hypertension, infantile hemangioma, abnormal stress, and ischemic heart failure. β-AR stimulation of tumor and stromal cells in the tumor microenvironment promotes tumor growth and metastasis and adversely affects survival. Drug repurposing or repositioning is defined as adapting or using an existing drug for a new indication in clinical use as it is or by making structural modifications. As cancer incidence increases worldwide, cancer treatment costs are also increasing. The focus of global cancer control is to reduce this cost and increase the effectiveness of cancer treatment. Beta-blockers inhibit the activation of downstream effectors and signaling pathways stimulated by β-AR stimulation. In addition, there is evidence of the anti-proliferative and apoptotic effects of beta-blockers on cancer cells. So far, repurposing studies of propranolol for breast cancer have yielded promising data. In this review, studies on repurposing drugs for cancer treatment, the mechanisms of action of beta-blockers on cancer cells, and use of these drugs in breast cancer treatment were evaluated. Increasing preclinical and clinical studies of repurposing drugs for breast cancer treatment, including beta-blockers, is critical to diversifying cancer treatment strategies and reducing costs.

Keywords:

Adrenergic receptor, breast cancer, cardiovascular drugs, catecholamine, drug repurposing, propranolol,

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