Advances in drug treatments for mesothelioma

Zucali, Paolo Andrea; Vincenzo, Fabio De; Perrino, Matteo; Digiacomo, Nunzio; Cordua, Nadia; D'Antonio, Federica; Borea, Federica; Fazio, Roberta; Pirozzi, Angelo; Santoro, Armando

doi:10.1080/14656566.2022.2072211

Cited by 2 publications

(4 citation statements)

References 86 publications

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“…Malignant mesothelioma (MM) is a rare and aggressive neoplasm originating from the mesothelial lining of the pleural cavity (1). Its annual incidence is globally increasing and it is closely related to asbestos exposure (accounting 80% of cases), with a long latency of almost 40 years between exposure and the disease onset.…”

Section: Introductionmentioning

confidence: 99%

“…The therapeutic landscape of mesothelioma is changing. In first line setting, platinum and pemetrexed chemotherapy has been the standard of care for unresectable disease since 2004 and no other treatments have been approved in the second-and third-line setting (1,5). However, the immunotherapy revolution has improved the survival outcomes of patients with a broad range of cancers, including mesothelioma.…”

Section: Introductionmentioning

confidence: 99%

“…In second line setting, nivolumab achieved a statistically significant improvement of both progression-free survival (PFS) and OS compared to placebo in pre-treated MM patients in the randomized, phase III, CONFIRM trial (8). Lastly, several ongoing phase III trials should provide robust evidence for any benefits from combining immunotherapy with chemotherapy in the first-line setting (1).…”

Section: Introductionmentioning

confidence: 99%

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Immunotherapy with immune checkpoint inhibitors and predictive biomarkers in malignant mesothelioma: Work still in progress

et al. 2023

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Malignant mesothelioma (MM) is a rare and aggressive neoplasm, usually associated with a poor prognosis (5 years survival rate <10%). For unresectable disease, platinum and pemetrexed chemotherapy has been the only standard of care in first line for more than two decades, while no standard treatments have been approved in subsequent lines. Recently, immunotherapy has revolutionized the therapeutic landscape of MM. In fact, the combination of ipilimumab plus nivolumab has been approved in first line setting. Moreover, immune checkpoint inhibitors (ICIs) showed promising results also in second-third line setting after platinum-based chemotherapy. Unfortunately, approximately 20% of patients are primary refractory to ICIs and there is an urgent need for reliable biomarkers to improve patient’s selection. Several biological and molecular features have been studied for this goal. In particular, histological subtype (recognized as prognostic factor for MM and predictive factor for chemotherapy response), programmed death ligand 1 (PD-L1) expression, and tumor mutational burden (widely hypothesized as predictive biomarkers for ICIs in several solid tumors) have been evaluated, but with unconclusive results. On the other hand, the deep analysis of tumor infiltrating microenvironment and the improvement in genomic profiling techniques has led to a better knowledge of several mechanisms underlying the MM biology and a greater or poorer immune activation. Consequentially, several potential biomarkers predictive of response to immunotherapy in patients with MM have been identified, also if all these elements need to be further investigated and prospectively validated.In this paper, the main evidences about clinical efficacy of ICIs in MM and the literature data about the most promising predictive biomarkers to immunotherapy are reviewed.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Immunotherapy with immune checkpoint inhibitors and predictive biomarkers in malignant mesothelioma: Work still in progress

et al. 2023

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“…Malignant mesothelioma is a tumor dramatically resistant to chemotherapy. Despite the introduction of modern therapeutic interventions, only modest changes in survival have been observed over time (2)(3)(4)(13)(14)(15)(16). Immunotherapy based on checkpoint blockade (ICB) is currently under investigation in clinical trials with -so far -disappointing results (17).…”

Section: Introductionmentioning

confidence: 99%

Important functional role of the protein osteopontin in the progression of malignant pleural mesothelioma

et al. 2023

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BackgroundMalignant Pleural Mesothelioma (MPM) is an aggressive cancer of the mesothelial lining associated with exposure to airborne non-degradable asbestos fibers. Its poor response to currently available treatments prompted us to explore the biological mechanisms involved in its progression. MPM is characterized by chronic non-resolving inflammation; in this study we investigated which inflammatory mediators are mostly expressed in biological tumor samples from MPM patients, with a focus on inflammatory cytokines, chemokines and matrix components.MethodsExpression and quantification of Osteopontin (OPN) was detected in tumor and plasma samples of MPM patients by mRNA, immunohistochemistry and ELISA. The functional role of OPN was investigated in mouse MPM cell lines in vivo using an orthotopic syngeneic mouse model.ResultsIn patients with MPM, the protein OPN was significantly more expressed in tumors than in normal pleural tissues and predominantly produced by mesothelioma cells; plasma levels were elevated in patients and associated with poor prognosis. However, modulation of OPN levels was not significantly different in a series of 18 MPM patients receiving immunotherapy with durvalumab alone or with pembrolizumab in combination with chemotherapy, some of whom achieved a partial clinical response. Two established murine mesothelioma cell lines: AB1 and AB22 of sarcomatoid and epithelioid histology, respectively, spontaneously produced high levels of OPN. Silencing of the OPN gene (Spp1) dramatically inhibited tumor growth in vivo in an orthotopic model, indicating that OPN has an important promoting role in the proliferation of MPM cells. Treatment of mice with anti-CD44 mAb, blocking a major OPN receptor, significantly reduced tumor growth in vivo.ConclusionThese results demonstrate that OPN is an endogenous growth factor for mesothelial cells and inhibition of its signaling may be helpful to restrain tumor progression in vivo. These findings have translational potential to improve the therapeutic response of human MPM.

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Advances in drug treatments for mesothelioma

Cited by 2 publications

References 86 publications

Immunotherapy with immune checkpoint inhibitors and predictive biomarkers in malignant mesothelioma: Work still in progress

Immunotherapy with immune checkpoint inhibitors and predictive biomarkers in malignant mesothelioma: Work still in progress

Important functional role of the protein osteopontin in the progression of malignant pleural mesothelioma

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