Pleural mesothelioma (PM) is deemed an uncommon tumor, resistant to chemotherapy with little chance of radical surgery and low survival rates. This review summarizes the latest advances in biomarker selection for diagnosis and drug treatment, based on search in Medline database carried out in the period between 1992 and 2020. The main prognostic and predictive biomarker is the histological subtype. The epithelioid neoplastic form is less aggressive than the sarcomatoid subtype and has a high sensitivity to chemotherapy, resulting in longer survival than sarcomatoid or biphasic subtypes of PM. Several biomarkers have been identified for the diagnosis of mesothelioma, but no mesothelial marker has a sensitivity of 100%. Therefore, panels of different biomarkers are needed, with positive and negative predictive value. New biomarkers emerging from the literature may be useful in differentiating reactive pleural processes from malignant ones and PMs from other neoplastic forms. In particular, the role of loss of expression of BAP1, MTAP and CDKN2A must be highlighted. The presence of frequent inactivating homozygous mutations of the BAP1 locus and the CDKN2A gene has been demonstrated by parallel massive sequencing in approximately 60% and 62% of cases respectively If simultaneous loss of BAP1 expression and homozygous deletion of CDKN2A or loss of expression of BAP1 and MTAP are present, sensitivity is much higher (92–100%). The new perspectives on therapy derive from studies conducted on BAP1 and other homologous recombination genes and from trials conducted on patients treated with immunotherapy. The inactivation of BAP1 could be used therapeutically, similarly to what has been shown in clinical studies conducted on patients with ovarian and prostate cancer with mutations in the DNA repair genes. In ongoing clinical trials, the recruitment of MPM patients will allow to assess the relationship between BAP1 genotype status and response to PARP inhibitors such as olaparib and niraparib. In addition, mesothelial cancer cells can express PDL1 especially in the epithelioid form and this expression is associated with a worse prognosis. PDL1 has also been evaluated in other tumor forms as an indicator of immunotherapy efficacy and seems to allow the best selection of patients affected by mesothelioma.
Biomarkers in the diagnosis and treatment of malignant pleural disease: an integrative review
Buttitta, Fiamma;Di Lorito, Alessia;D'Angelo, Emanuela
2020-01-01
Abstract
Pleural mesothelioma (PM) is deemed an uncommon tumor, resistant to chemotherapy with little chance of radical surgery and low survival rates. This review summarizes the latest advances in biomarker selection for diagnosis and drug treatment, based on search in Medline database carried out in the period between 1992 and 2020. The main prognostic and predictive biomarker is the histological subtype. The epithelioid neoplastic form is less aggressive than the sarcomatoid subtype and has a high sensitivity to chemotherapy, resulting in longer survival than sarcomatoid or biphasic subtypes of PM. Several biomarkers have been identified for the diagnosis of mesothelioma, but no mesothelial marker has a sensitivity of 100%. Therefore, panels of different biomarkers are needed, with positive and negative predictive value. New biomarkers emerging from the literature may be useful in differentiating reactive pleural processes from malignant ones and PMs from other neoplastic forms. In particular, the role of loss of expression of BAP1, MTAP and CDKN2A must be highlighted. The presence of frequent inactivating homozygous mutations of the BAP1 locus and the CDKN2A gene has been demonstrated by parallel massive sequencing in approximately 60% and 62% of cases respectively If simultaneous loss of BAP1 expression and homozygous deletion of CDKN2A or loss of expression of BAP1 and MTAP are present, sensitivity is much higher (92–100%). The new perspectives on therapy derive from studies conducted on BAP1 and other homologous recombination genes and from trials conducted on patients treated with immunotherapy. The inactivation of BAP1 could be used therapeutically, similarly to what has been shown in clinical studies conducted on patients with ovarian and prostate cancer with mutations in the DNA repair genes. In ongoing clinical trials, the recruitment of MPM patients will allow to assess the relationship between BAP1 genotype status and response to PARP inhibitors such as olaparib and niraparib. In addition, mesothelial cancer cells can express PDL1 especially in the epithelioid form and this expression is associated with a worse prognosis. PDL1 has also been evaluated in other tumor forms as an indicator of immunotherapy efficacy and seems to allow the best selection of patients affected by mesothelioma.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
