Preclinical studies identify novel targeted pharmacological strategies for treatment of human malignant pleural mesothelioma

Roberto E. Favoni, Antonio Daga, Paolo Malatesta, Tullio Florio

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The incidence of human malignant pleural mesothelioma (hMPM) is still increasing worldwide. hMPM prognosis is poor even if the median survival time has been slightly improved after the introduction of the up-to-date chemotherapy. Nevertheless, large phase II/III trials support the combination of platinum derivatives and pemetrexed or raltitrexed, as preferred first-line schedule. Better understanding of the molecular machinery of hMPM will lead to the design and synthesis of novel compounds targeted against pathways identified as crucial for hMPM cell proliferation and spreading. Among them, several receptors tyrosine kinase show altered activity in subsets of hMPM. This observation suggests that these kinases might represent novel therapeutic targets in this chemotherapy-resistant disease. Over these foundations, several promising studies are ongoing at preclinical level and novel molecules are currently under evaluation as well. Yet, established tumour cell lines, used for decades to investigate the efficacy of anticancer agents, although still the main source of drug efficacy studies, after long-term cultures tend to biologically diverge from the original tumour, limiting the predictive potential of in vivo efficacy. Cancer stem cells (CSCs), a subpopulation of malignant cells capable of self-renewal and multilineage differentiation, are believed to play an essential role in cancer initiation, growth, metastasization and relapse, being responsible of chemo- and radiotherapy refractoriness. According to the current carcinogenesis theory, CSCs represent the tumour-initiating cell (TIC) fraction, the only clonogenic subpopulation able to originate a tumour mass. Consequently, the recently described isolation of TICs from hMPM, the proposed main pharmacological target for novel antitumoural drugs, may contribute to better dissect the biology and multidrug resistance pathways controlling hMPM growth.

Original languageEnglish
Pages (from-to)532-553
Number of pages22
JournalBritish Journal of Pharmacology
Volume166
Issue number2
DOIs
Publication statusPublished - May 2012

Fingerprint

Pharmacology
Neoplastic Stem Cells
Drug Therapy
Therapeutics
Pemetrexed
Neoplasms
Receptor Protein-Tyrosine Kinases
Multiple Drug Resistance
Growth
Malignant Mesothelioma
Platinum
Tumor Cell Line
Pharmaceutical Preparations
Antineoplastic Agents
Appointments and Schedules
Carcinogenesis
Phosphotransferases
Radiotherapy
Cell Proliferation
Recurrence

Keywords

  • cytotoxic drugs
  • in vitro studies
  • pleural mesothelioma
  • targeted compounds
  • tumour-initiating cells

ASJC Scopus subject areas

  • Pharmacology

Cite this

Preclinical studies identify novel targeted pharmacological strategies for treatment of human malignant pleural mesothelioma. / Favoni, Roberto E.; Daga, Antonio; Malatesta, Paolo; Florio, Tullio.

In: British Journal of Pharmacology, Vol. 166, No. 2, 05.2012, p. 532-553.

Research output: Contribution to journalArticle

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