Scientific Advances and New Frontiers in Mesothelioma Therapeutics

Mutti, Luciano; Peikert, Tobias; Robinson, B. W.; Scherpereel, Arnaud; Tsao, Anne S.; Perrot, Marc de; Woodard, Gavitt A.; Jablons, David M.; Wiens, Jacinta; Hirsch, Fred R.; Yang, Haining; Carbone, Michele; Thomas, Anish; Hassan, Raffit

doi:10.1016/j.jtho.2018.06.011

Cited by 92 publications

(90 citation statements)

References 126 publications

(129 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Clinical trials using cytotoxic T‐lymphocyte–associated protein 4 (CTLA‐4) inhibitors failed to improve survival in mesothelioma . Subsequent trials suggested that PD‐L1 inhibitors may benefit some patients .…”

Section: Treatmentmentioning

confidence: 99%

“…A priority is the identification of biomarkers that predict benefit or harm from immune checkpoint inhibitors. Reported toxicities are comparable to the use of immunotherapy in other tumors and can be managed with the standard of care . Other aspects of the antitumor immune response are being targeted in smaller studies and include vaccines, autologous T cells, chimeric antigen receptor T cells, and viral therapies.…”

Section: Treatmentmentioning

confidence: 99%

See 1 more Smart Citation

Mesothelioma: Scientific clues for prevention, diagnosis, and therapy

Carbone

Adusumilli

Alexander

et al. 2019

CA A Cancer J Clinicians

Self Cite

359

488

View full text Add to dashboard Cite

Mesothelioma affects mostly older individuals who have been occupationally exposed to asbestos. The global mesothelioma incidence and mortality rates are unknown, because data are not available from developing countries that continue to use large amounts of asbestos. The incidence rate of mesothelioma has decreased in Australia, the United States, and Western Europe, where the use of asbestos was banned or strictly regulated in the 1970s and 1980s, demonstrating the value of these preventive measures. However, in these same countries, the overall number of deaths from mesothelioma has not decreased as the size of the population and the percentage of old people have increased. Moreover, hotspots of mesothelioma may occur when carcinogenic fibers that are present in the environment are disturbed as rural areas are being developed. Novel immunohistochemical and molecular markers have improved the accuracy of diagnosis; however, about 14% (high-resource countries) to 50% (developing countries) of mesothelioma diagnoses are incorrect, resulting in inadequate treatment and complicating epidemiological studies. The discovery that germline BRCA1-asssociated protein 1 (BAP1) mutations cause mesothelioma and other cancers (BAP1 cancer syndrome) elucidated some of the key pathogenic mechanisms, and treatments targeting these molecular mechanisms and/or modulating the immune response are being tested. The role of surgery in pleural mesothelioma is controversial as it is difficult to predict who will benefit from aggressive management, even when local therapies are added to existing or novel systemic treatments. Treatment outcomes are improving, however, for peritoneal mesothelioma. Multidisciplinary international collaboration will be necessary to improve prevention, early detection, and treatment. CA Cancer J Clin 2019;69:402-429.

show abstract

Section: Treatmentmentioning

confidence: 99%

Section: Treatmentmentioning

confidence: 99%

Mesothelioma: Scientific clues for prevention, diagnosis, and therapy

Carbone

Adusumilli

Alexander

et al. 2019

CA A Cancer J Clinicians

Self Cite

359

488

View full text Add to dashboard Cite

show abstract

“…The standard treatment for unresectable, advanced malignant mesothelioma is chemotherapy, although with a very poor prognosis. 36 Similar to its use in non-smallcell lung cancer, 37-44 cisplatin (CDDP) and pemetrexed (PEM) combination therapy (CDDP/PEM) approved by the US Food and Drug Administration (FDA) in 2004, is strongly recommended as the first-line treatment for mesothelioma. 45 Moreover, molecularly targeted agents have been developed to augment cytotoxic chemotherapy.…”

Section: Icis In the First-line Settingsmentioning

confidence: 99%

Current evidence and future perspectives of immune-checkpoint inhibitors in unresectable malignant pleural mesothelioma

Hotta

Fujimoto

2020

J Immunother Cancer

View full text Add to dashboard Cite

Platinum-based chemotherapy is commonly used as the standard first-line treatment for unresectable malignant pleural mesothelioma (MPM). However, in recent times, immune-checkpoint inhibitors (ICIs) have led to a paradigm shift. Herein, we review relevant literature and ongoing trials of ICIs used as both first-line and salvage therapies. Specifically, in the Japanese single-arm, phase II trial, the MERIT trial, nivolumab, an antiprogrammed cell death 1 (PD-1) antibody showed favorable efficacy when used as a salvage therapy. Currently, multiple ICI monotherapy or combination therapy trials have been conducted, which could provide further evidence. Among available ICIs, the anti-PD-1 antibody is promising for unresectable MPM, despite the limited efficacy of anti-CTLA4 monotherapy. Ongoing studies will further confirm the potential efficacy of ICIs for MPM, as observed across other malignancies. It is also crucial to identify any clinically useful predictive biomarkers that could reveal ICIs with maximal effects in MPM.

show abstract

“…Even if the use of asbestos is now banned in several countries, the mean latency period between asbestos exposures to the time of mesothelioma diagnosis has been determined to range between 20 and 40 years (H. H. Sun et al, ). Due to this long latency, it is expected that, in the next decades, asbestos‐induced mesothelioma incidence will persist (Mutti et al, ).…”

Section: Introductionmentioning

confidence: 99%

Data mining analysis of the PP2A cell cycle axis in mesothelioma patients

Pippa

Boffo

Odero

et al. 2019

Journal Cellular Physiology

View full text Add to dashboard Cite

Mesothelioma is an aggressive tumor that affects thousands of people every year. The therapeutic options for patients are limited; hence, a better understanding of mesothelioma biology is crucial to improve patient survival. To find new molecular targets and therapeutic strategies related to the protein phosphatase 2A (PP2A) network, we analyzed the gene expression of known PP2A inhibitors in mesothelioma patient samples. Our analysis disclosed a general overexpression of all PP2A‐negative regulators in mesothelioma patients. Moreover, the expression of ANP32E and CIP2A genes, increased in 16% and 11% of cases, positively correlates with the ones of all the other PP2A regulators and the ones of the main cyclins and CDKs, suggesting the existence of a feed‐forward loop that might contribute to the mesothelioma progression via PP2A inactivation. Overall, our study indicates the existence of a strategic and targetable axis between PP2A inhibitors (ANP32E and CIP2A) and cell cycle regulators (cyclin B2/CDK1) and provides a valuable rationale for using a personalized combinational therapy approach to improve mesothelioma patient survival.

show abstract

Scientific Advances and New Frontiers in Mesothelioma Therapeutics

Cited by 92 publications

References 126 publications

Mesothelioma: Scientific clues for prevention, diagnosis, and therapy

Mesothelioma: Scientific clues for prevention, diagnosis, and therapy

Current evidence and future perspectives of immune-checkpoint inhibitors in unresectable malignant pleural mesothelioma

Data mining analysis of the PP2A cell cycle axis in mesothelioma patients

Contact Info

Product

Resources

About