Tumor hypoxia: The major culprit behind cisplatin resistance in cancer patients

Cisplatin is the most commonly used first-line drug for cancer treatment. However, many patients develop resistance to cisplatin therapy which ultimately results in therapy failure and increased mortality. A growing body of evidence shows that the hypoxic microenvironment is the prime factor underlying tumor insensitivity to cisplatin treatment. Since tumors in the majority of cancer patients are under hypoxic stress (low oxygen supply), it becomes necessary to understand the pathobiology behind hypoxia-induced cisplatin resistance in cancer cells. Here, we discuss the molecular events that render hypoxic tumors insensitive to cisplatin therapy. Furthermore, various drugs and tumor oxygenation techniques have been developed to circumvent cisplatin resistance in hypoxic tumors. However, their pharmaceutical applications are limited due to failures in clinical investigations and a lack of preclinical studies in the hypoxic tumor microenvironment. This review addresses these challenges and provides new directions for the strategic deployment of cisplatin sensitizers in the hypoxic tumor microenvironment.

Automated summary

Cisplatin resistance in cancer treatment is often due to the hypoxic microenvironment in tumors, which leads to insensitivity. Understanding the molecular events behind hypoxia-induced cisplatin resistance is crucial in overcoming treatment failure. Various strategies have been developed to overcome cisplatin resistance in hypoxic tumors, but further clinical investigations and preclinical studies are needed to improve their pharmaceutical applications.