Cisplatin in Ovarian Cancer Treatment—Known Limitations in Therapy Force New Solutions

Abstract

Cisplatin is one of the most commonly used anticancer drugs worldwide. It is mainly used in the treatment of ovarian cancer, but also used in testicular, bladder and lung cancers. The significant advantage of this drug is the multidirectional mechanism of its anticancer action, with the most important direction being damaging the DNA of cancer cells. Unfortunately, cisplatin displays a number of serious disadvantages, including toxicity to the most important organs, such as kidneys, heart, liver and inner ear. Moreover, a significant problem among patients with ovarian cancer, treated with cisplatin, is the development of numerous resistance mechanisms during therapy, including changes in the processes of cellular drug import and export, changes in the DNA damage repair mechanisms, as well as numerous changes in the processes of apoptosis and autophagy. Due to all of the mentioned problems, strategies to increase the effectiveness of cisplatin in the treatment of ovarian cancer are intensively sought. The most important strategy includes the development of less toxic cisplatin analogs. Another important direction is combination therapy, involving the simultaneous use of cisplatin with different anticancer drugs, substances derived from plants, temperature or radiotherapy. Many years of observations accompanying the presence of cisplatin in the therapy made it possible to provide a series of verifiable, statistically significant data, but also to show how, over time, with the new information and scientific discoveries, it is possible to describe and understand the therapeutic problems observed in practice, such as the acquisition of drug resistance by tumor cells or induction of changes in the tumor microenvironment. According to the authors, confronting what we knew so far with what new trends offer has a profound meaning. This paper presents information on the history of cisplatin and describes the molecular mechanisms of its action and the development of resistance by cancer cells. In addition, our goal was to highlight a number of therapeutic strategies to increase the effectiveness of cisplatin in the treatment of ovarian cancer, as well as to identify methods to eliminate problems associated with the use of cisplatin.

Metal–Organic Frameworks for Cisplatin Delivery to Cancer Cells: A Molecular Dynamics Simulation

“… 1 , 2 Cisplatin was first synthesized by Peyrone in 1845. 3 Its properties were fortuitously discovered in 1965 by Dr. Barnett Rosenberg while observing electric current effects on bacterial growth. 4 , 5 Rosenberg reported that electric fields lead to filamentous growth of Escherichia coli cells.…”

Evidence of direct interaction between cisplatin and the caspase‐cleaved prostate apoptosis response‐4 tumor suppressor

“…The platinum‐containing compound cisplatin is one of the most widely employed of these agents (Bukowski et al, 2020 ; Qi et al, 2019 ). Cisplatin [ cis ‐diamminedichloroplatinum (II)] was approved as a cancer therapeutic in 1978 (Makovec, 2019 ) and has shown broad‐spectrum effectiveness: it has been used to treat cancers of the lung, ovaries, breast, and brain, among others (Dasari & Tchounwou, 2014 ; Makovec, 2019 ; Zoń & Bednarek, 2023 ). The therapeutic strategy of cisplatin is to target the rapidly dividing DNA of cancer cells, where it binds preferentially to the N7 position of purine bases.…”

“…Despite its effectiveness as an affordable standard therapy for various tumors, cisplatin's utility is limited by the development of drug resistance and its accumulation in tissues, which can lead to severe side effects such as neurotoxicity, ototoxicity, and nephrotoxicity (Martinho et al, 1898 ; Messori & Merlino, 2014 ; Mortensen et al, 2020 ; Peleg‐Shulman et al, 2002 ; Zhao et al, 2014 ; Zoń & Bednarek, 2023 ). Several cisplatin analogs have been developed for use in the treatment of cancers (Dasari & Tchounwou, 2014 ; Kopacz‐Bednarska & Król, 2022 ).…”

Silencing of KIF2C enhances the sensitivity of hepatocellular carcinoma cells to cisplatin through regulating the PI3K/AKT/MAPK signaling pathway

“…Cisplatin is a chemotherapeutic agent widely used in cancer treatment [12] and is considered a representative member of the platinum compound family. Since the 1970s, cisplatin has been widely used to treat a variety of malignancies, including lung, ovarian, bladder, and HCCs [13]. However, a remarkable variation was found in patient response to cisplatin, suggesting a possible underlying molecular mechanism regulating its sensitivity.…”