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CONCLUSION
With a growing understanding of the molecular underpinnings of DPM, there has been a multitude of
rationally designed clinical trials looking to exploit potential therapeutic vulnerabilities. Newer generations
of agents, including CAR-T therapies targeting mesothelin and arginine-deprivation therapies for ASS1
deficient mesotheliomas, hold particular promise, and aim to overcome the historically poor response rates
in targeted therapies for mesothelioma.

The preponderance of disappointing trial results described here, however, highlights the struggle to translate
promising preclinical data into patient care. To propel the field forward, we must continue to collaborate to
establish preclinical models that faithfully recapitulate DPM biology for in vivo testing and strive to better
[134]
refine biomarkers and patient selection criteria for trials of targeted therapy in DPM. Investigation of several
promising preclinical targets (e.g., microRNAs) is underway but has not yet been translated into clinical
[135]
investigation ; Future trials need to incorporate comprehensive pathologic, genomic, and expression level
data of enrolled patients to better understand those who benefit from a treatment and refine future trial
[136]
designs . To accomplish this will require building platforms for close iterative collaboration between
medical and surgical oncologists, pathologists, and laboratory-based genomic and pharmacologic scientists;
this investment is critical to improving therapeutic options for patients with DPM.

DECLARATIONS
Authors’ contributions
The following authors made substantial contributions to the conception and design of the work, literature
review, technical support, and writing of the work: Offin M, Fitzgerald B, Zauderer MG, Doroshow D

Availability of data and materials
Not applicable.

Financial support and sponsorship
This research was supported in part by the NIH/NCI (P30 CA008748).

Conflicts of interest
Michael Offin has consulted with Novartis, Jazz, and PharmaMar regarding oncology drug development.
Michael Offin has received an honorarium from Targeted Oncology, OncLive, and the American Society for
Radiation Oncology.
Bailey Fitzgerald has no relevant conflicts to declare.
Marjorie G. Zauderer has received consulting fees from Ikena, Takeda, GlaxoSmithKline, Aldeyra
Therapeutics, and Novocure and honoraria for CME content from PER, Medscape, Research to Practice,
Medical Learning Institute and OncLive. Memorial Sloan Kettering receives research funding from the
Department of Defense, the National Institutes of Health, Precog, GlaxoSmithKline, Epizyme, Polaris, Sellas
Life Sciences, Bristol Myers Squibb, Millenium/Takeda, Curis, and Atara for research conducted by
Marjorie G. Zauderer. Marjorie G. Zauderer serves as Chair of the Board of Directors of the Mesothelioma
Applied Research Foundation, an uncompensated position.
Deborah Doroshow has received consulting fees from AstraZeneca and Mirati Therapeutics and honoraria
from PER, OncLive, and Targeted Oncology.

Ethical approval and consent to participate
Not applicable.