Cisplatin in Liver Cancer Therapy

Abstract

Hepatocellular carcinoma (HCC) is the most common primary liver tumor and is often diagnosed at an unresectable advanced stage. Systemic chemotherapy as well as transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) are used to treat advanced HCC. TACE and HAIC have long been the standard of care for patients with unresectable HCC but are limited to the treatment of intrahepatic lesions. Systemic chemotherapy with doxorubicin or chemohormonal therapy with tamoxifen have also been considered, but neither has demonstrated survival benefits. In the treatment of unresectable advanced HCC, cisplatin is administered transhepatic arterially for local treatment. Subsequently, for cisplatin-refractory cases due to drug resistance, a shift to systemic therapy with a different mechanism of action is expected to produce new antitumor effects. Cisplatin is also used for the treatment of liver tumors other than HCC. This review summarizes the action and resistance mechanism of cisplatin and describes the treatment of the major hepatobiliary cancers for which cisplatin is used as an anticancer agent, with a focus on HCC.

Glycyrrhetinic Acid as a Hepatocyte Targeting Ligand-Functionalized Platinum(IV) Complexes for Hepatocellular Carcinoma Therapy and Overcoming Multidrug Resistance

“…5,6 However, the application of platinum(II)-based agents in clinical practice for treatment of patients with HCC has been largely limited owing to the high systemic toxicity and poor selectivity. 7,8 Unfortunately, the appearance of acquired drug resistance leads HCC patients to show a poor drug response, which is another important factor restricting its chemotherapy success. 9,10 Therefore, the development of a new valid therapeutic approach to improve therapeutic effect and conquer the off-target effects of cisplatin in addition to reverse multidrug resistance is extremely critical for HCC treatment.…”

“…Hepatocellular carcinoma (HCC) is one of the most common malignancy characterized by high morbidity and mortality together with high recurrence rates and distant metastasis, resulting about a million cancer-related deaths every year. − In addition to hepatectomy and liver transplantation, chemotherapy is mainly used as a treatment option to date. It is well-known that platinum(II)-based antitumor agents, such as cisplatin (CDDP, Figure ) and its analogues (e.g., oxaliplatin and carboplatin), have been administered in single or combination regimens used to treat various solid tumors in the clinic, including HCC. , However, the application of platinum(II)-based agents in clinical practice for treatment of patients with HCC has been largely limited owing to the high systemic toxicity and poor selectivity. , Unfortunately, the appearance of acquired drug resistance leads HCC patients to show a poor drug response, which is another important factor restricting its chemotherapy success. , Therefore, the development of a new valid therapeutic approach to improve therapeutic effect and conquer the off-target effects of cisplatin in addition to reverse multidrug resistance is extremely critical for HCC treatment.…”

Increasing evidence for the efficacy of hepatic arterial infusion chemotherapy combined with systemic therapy for advanced hepatocellular carcinoma with macrovascular invasion: time to consider a more effective approach

“…Drug therapy is classified into (I) chemotherapy, (II) molecular targeted therapy, and (III) immune-mediated therapy. Chemotherapy is initiated solely or in combination with surgical treatment, radiation therapy, or other drug therapies, depending on the cancer type and progression ( 11 ). By transporting cytotoxic chemical agents directly into the tumor-feeding arteries, HAIC bears higher local concentration, more substantial antitumor efficacy, and lower systemic toxicity ( 2 ).…”

“…Several antitumor chemical agents are applied for advanced HCC. Cisplatin was the first platinum drug approved as an anticancer agent in the 1970s and has been used worldwide to treat >80% of cancers ( 11 ). Because it damages not only cancer cells but also normal cells, systemic toxicity and the development of resistance limit its use.…”

“…Because it damages not only cancer cells but also normal cells, systemic toxicity and the development of resistance limit its use. Cisplatin has various adverse effects such as digestive disorders, myelosuppression, nephrotoxicity, ototoxicity, and neurotoxicity ( 11 ). Ototoxicity frequently occurs and is irreversible, which indicates that is easily affects patients’ quality of life.…”