Research progress in strategies to improve the efficacy and safety of doxorubicin for cancer chemotherapy

ABSTRACT

Introduction

DOX exerts strong anticancer activity and is commonly used to treat different cancers, including bone sarcomas, soft tissues, bladder, ovary, stomach, thyroid, breast, acute lymphoblastic leukemia, Hodgkin lymphoma, lung cancer, and myeloblastic leukemia. However, the cumulative doses of DOX above 550mg/m2 cause irreversible cardiotoxicity and other severe adverse effects. In this context, concerning DOX, several patents have been published in the last two decades. This activity highlights various aspects of DOX, such as registered patent analysis, pharmacological action, toxicityminimization, formulation development such as those approved by FDA, under clinical trials, and newly developed nano-delivery systems.

Areas covered

This review analyzes the different aspects of DOX-based chemotherapeutics and the development of drug delivery systems in theliterature published from 2000 to early 2020.

Expert opinion

DOX-based chemotherapy is still few steps away from being “perfect and safe” therapy. Certain severe systemic side effects are associated with DOX therapy. It is expected that, in the near future, DOX therapy can be much effective by selecting an ideal nanocarrier system, DOX conjugates, proper structural modifications, DOX-immunotherapy, and combination therapy. The advanced formulationsof DOX from the registered patents and recent research articles need clinical trials to bring safe treatment for cancer patients.

KEYWORDS:

• Doxorubicin
• cancer
• chemotherapy
• nano-formulations
• efficacy and safety

Article highlights

• Doxorubicin is the most frequently used chemotherapeutic drug.

• Doxorubicin kills tumor cells by inhibiting topoisomerase II enzyme and block DNA synthesis.

• Severe and life-threatening systemic adverse effects are associated with doxorubicin therapy.

• Nano delivery system improved systemic toxicity of doxorubicin.

• We are focusing on selective targeting of tumor cells and minimizing the damage of healthy tissues.

• Different techniques for improving DOX efficacy.

• Combination therapy of doxorubicin with other drugs improved its efficacy.

Additional information

Funding

This paper was funded by the Natural Science Foundation of Shandong Province, China and Key Project for Technology Research and Development of Shandong Province, China (grant numbers ZR2017MH061, ZR2019MB054).