Section 3 Emerging Drugs

**45**

**Chapter 4**

**Abstract**

hippo signaling.

**1. Introduction**

combinations, NF2 mutations, BAP1 mutations

Mesothelioma

Emerging Drug Therapies for

*Derek B. Oien, Jeremy Chien, Julian Molina and Viji Shridhar*

The systemic chemotherapy combination of cisplatin and pemetrexed has been the mesothelioma standard of care for well over a decade. This regimen has only achieved a disappointing overall median survival of about 1 year. Improved survival has been reported when systemic chemotherapy is combined with surgery and radiotherapy, and for using localized chemotherapy in some cases. The choice of mesothelioma treatment often depends on the anatomical location, histologic subtype, and disease progression. Several experimental drugs have also been investigated in mesothelioma, often with limited positive results that maintain the reputation of mesothelioma as a graveyard for drug development. This chapter will review the use of drug treatment in mesothelioma and highlight emerging experimental drug therapies in clinical trials. Experimental drugs for mesothelioma include inhibitors for checkpoints, epidermal growth factor, AXL, focal adhesion kinase, vascular endothelial growth factor, poly-ADP-ribose-polymerase, and

**Keywords:** targeted drugs, experimental therapeutics, molecular therapies, drug

The treatment of mesothelioma currently varies by primary origin of the tumor, histologic subtype, and disease progression. The most common mesothelioma is malignant pleural mesothelioma (about 80% of cases) [1]. Research for new drug treatments are often investigated in pleural mesothelioma and later extrapolated to less common types such as peritoneal mesothelioma (about 10% of cases). Both of these mesothelioma types have the same three subtypes of epithelioid, sarcomatoid, and biphasic histology. Biphasic mesothelioma is a combination of epithelioid and sarcomatoid histology, each contributing to at least 10% of the tissue [2]. Mesothelioma tends to spread regionally, then into the alternate thoracic lobe for pleural mesothelioma or across the abdomen for peritoneal mesothelioma, and can metastasize across the diaphragm or as distant metastases [2, 3]. Distant metastases were found in a postmortem study in over half of the 318 pleural mesothelioma patients examined, while distant metastasizes of peritoneal mesothelioma are not as common [2, 4]. Surgery is more common when disease is diagnosed early and tumors are resectable, but most patients are diagnosed at later stages of disease when they are not candidates. For pleural mesothelioma, extrapleural pneumonectomy and pleurectomy/decortication are the most common nonpalliative procedures for tumors that are confined to the excised region [5]. Some of these patients

### **Chapter 4**
