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Recombinant human endostatin as a potential anti-angiogenic agent: therapeutic perspective and current status

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Abstract

Angiogenesis is the physiological process that results in the formation of new blood vessels develop from pre-existing vasculature and plays a significant role in several physiological and pathological processes. Inhibiting angiogenesis, a crucial mechanism in the growth and metastasis of cancer, has been proposed as a potential anticancer therapy. Different studies showed the beneficial effects of angiogenesis inhibitors either in patients suffering from different cancers, alone or in combination with conventional therapies. Even though there are currently a number of efficient anti-angiogenic drugs, including monoclonal antibodies and kinase inhibitors, the associated toxicity profile and their affordability constraints are prompting researchers to search for a safe and affordable angiostatic agent for cancer treatment. Endostatin is one of the endogenous anti-angiogenic candidates that have been extensively pursued for the treatment of cancer, but even over three decades after its discovery, we have not made much advancement in employing it as an anticancer therapeutic despite of its remarkable anti-angiogenic effect with low toxicity profile. A recombinant human endostatin (rh-Es) variant for non-small cell lung cancer was approved by China in 2006 and has since been used effectively. Several other successful clinical trials related to endostatin for various malignancies are either ongoing or have already been completed with promising results. Thus, in this review, we have provided an overview of existing anti-angiogenic drugs developed for cancer therapy, with a summary of tumour angiogenesis in the context of Endostatin, and clinical status of rh-Es in cancer treatment. Furthermore, we briefly discuss the various strategies to improve endostatin features (poor pharmacokinetic properties) for developing rh-Es as a safe and effective agent for cancer treatment.

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Abbreviations

Bfgf:

Basic fibroblast growth factor

CBR:

Clinical beneficial rate

EC:

Endothelial cells

ECM:

Extracellular matrix

FDA:

Food and Drug Administration

FGF:

Fibroblast growth factor

HCC:

Hepatocellular carcinoma

HIF:

Hypoxia-inducible factor

HELP:

Half-life extension partners

IFN:

Interferon

KI:

Kinase inhibitor

mAb:

Monoclonal antibodies

MMP:

Matrix metalloproteinase

NMPA:

National Medical Products Administration

NSCLC:

Non-small cell lung cancer

OS:

Overall survival

PCH:

Pulmonary capillary hemangiomatosis

PEG:

Polyethylene glycol

PK:

Pharmacokinetic

rh-Es:

Recombinant human endostatin

RPLS:

Reversible posterior leukoencephalopathy syndrome

RNA:

Ribonucleic acids

SFDA:

State Food and Drug Administration of China

SPARC:

Secreted Protein Acidic And Cysteine Rich

TGF:

Transforming growth factor

TNF:

Tumour necrosis factor

TS-2:

Transglutaminase-2

TSP-1:

Thrombospondin-1

VEGF:

Vascular endothelial growth factor

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  1. Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Mohali, Punjab, 160062, India

    J. Anakha, Prakashkumar Dobariya & Abhay H. Pande

  2. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Mohali, Punjab, 160062, India

    Shyam Sunder Sharma

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Anakha, J., Dobariya, P., Sharma, S.S. et al. Recombinant human endostatin as a potential anti-angiogenic agent: therapeutic perspective and current status. Med Oncol 41, 24 (2024). https://doi.org/10.1007/s12032-023-02245-w

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