Soluble Mesothelin, Megakaryocyte Potentiating Factor, and Osteopontin as Markers of Patient Response and Outcome in Mesothelioma

Hollevoet, Kevin; Nackaerts, Kristiaan; Gosselin, Robert; Wever, Walter De; Bosquee, Lionel; Vuyst, Paul De; Germonpré, Paul; Kellen, Eliane; Legrand, Catherine; Kishi, Yoshiro; Delanghe, Joris; Meerbeeck, Jan P. van

doi:10.1097/jto.0b013e3182272294

Cited by 73 publications

(85 citation statements)

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“…Regarding response to treatment, in contrast to mesothelin and MPF which decrease shortly after resection, osteopontin increases [39]. This probably highlights the effect of wound healing and tissue remodelling on osteopontin levels.…”

Section: Osteopontinmentioning

confidence: 92%

“…Mesothelin measurement may be helpful to overcome this problem. If confirmed in larger series, mesothelin or MPF could be used as an adjunct to radiological monitoring in patients with epithelioid or mixed MM [39].…”

Section: Discussionmentioning

confidence: 99%

“…Two recent studies suggested that a 10% change in mesothelin levels above baseline values is significant [36,37], whereas others proposed a threshold of 25% [38]. HOLLEVOET et al [39] suggested a 15% threshold to avoid interference with ELISA variance, which can be up to 12%.…”

Section: Treatment Monitoring Performancementioning

confidence: 99%

“…When radiological response was compared with the changes in serum mesothelin, MPF and plasma osteopontin levels demonstrated that osteopontin levels were less closely associated with the radiological responses compared to those of mesothelin and MPF. However, a link between higher blood osteopontin level and patient's shorter survival has been reported, but extensive validation is absent [28,39].…”

Section: Osteopontinmentioning

confidence: 99%

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Effectiveness of mesothelin family proteins and osteopontin for malignant mesothelioma: Table 1–

et al. 2012

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Malignant mesothelioma (MM) is an aggressive tumour with poor prognosis whose early diagnosis is difficult. Mesothelin, megakaryocyte potentiating factor (MPF) and osteopontin have attracted attention as biomarkers. The aim of the present review is to provide an overview regarding these candidate biomarkers for MM, and discuss their potential role in today's clinical practice.Mesothelin and MPF have good specificity but sub-optimal sensitivity for detection of MM, being negative both in the sarcomatoid histological sub-type and in almost half of epithelioid mesothelioma, especially in the early stages. Osteopontin is a marker of the duration of asbestos exposure, but lacks specificity for mesothelioma. Several patient characteristics influence the diagnostic accuracy of biomarkers and make the establishment of the ''optimal'' diagnostic threshold difficult. Mesothelin and MPF have proved useful in assessing response to treatment. Combining different markers together may lead to an improvement in diagnostic accuracy, but there is still need for research in this area. Extensive validation and further research is required to improve the use of serum markers in mesothelioma management. In the near future, their application in clinical practice is probably in monitoring response to therapy, rather than in guiding diagnostic decisions and risk assessment of asbestos-exposed populations.

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Section: Osteopontinmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Treatment Monitoring Performancementioning

confidence: 99%

Section: Osteopontinmentioning

confidence: 99%

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Effectiveness of mesothelin family proteins and osteopontin for malignant mesothelioma: Table 1–

et al. 2012

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“…Other studies (8)(9)(10)(11)(12)(13)(14) confirmed that serum SMRP was a promising marker for diagnosis, prognosis and clinical monitoring of MPM. High SMRP concentrations were detected in all the studies only in the epithelioid and mixed MPM.…”

Section: Soluble Mesothelin-related Peptides (Smrp)mentioning

confidence: 88%

Serum mesothelin and other biomarkers: what have we learned in the last decade?

et al. 2018

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In the last decade there is been much interest in noninvasive, economic and well-accepted diagnostic tests for screening of subjects exposed to asbestos, and in patients with malignant pleuric mesothelioma (MPM) for diagnosis or monitoring response to treatment. Several biomarkers have been suggested as tools for screening and early diagnosis of MPM. Currently, in patients with MPM, have been reported high levels of soluble mesothelin-related peptides (SMRP), plasmatic osteopontin (pOPN), vimentin, fibulin-3 and many others as promising marker for diagnosis, even their use in prevention monitoring is still discussed. In this type of disease, a key role could be played by miRNAs, which expression has been investigated in a large series of MPM to examine new pathways useful in diagnosis, prognosis and therapy. An altered expression of some proteins has been reported, useful as biomarkers, in comparative proteomic analysis of malignant pleural mesothelioma. New promising markers are nowadays under study and alone or better in combination, they'll be very helpful in diagnosing, monitoring mesothelioma patients or for screening of risk groups.

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Phase 1 study of the antimesothelin immunotoxin SS1P in combination with pemetrexed and cisplatin for front‐line therapy of pleural mesothelioma and correlation of tumor response with serum mesothelin, megakaryocyte potentiating factor, and cancer antigen 125

Hassan

Sharon

Thomas

et al. 2014

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BACKGROUND The primary objective of this study was to determine the safety and maximum tolerated dose (MTD) of the antimesothelin immunotoxin SS1(dsFv)PE38 (SS1P) (a recombinant antimesothelin immunotoxin consisting of a murine antimesothelin variable antibody fragment [Fv] linked to PE38, a truncated portion of Pseudomonas exotoxin A) in combination with pemetrexed and cisplatin in chemotherapy‐naive patients with advanced malignant pleural mesothelioma (MPM). Secondary objectives included tumor response, SS1P pharmacokinetics, and serum biomarkers of response. METHODS Chemotherapy‐naive patients with stage III or IV, unresectable, epithelial or biphasic MPM and normal organ functions were eligible. Pemetrexed (500 mg/m2 on day 1) and cisplatin (75 mg/m2 on day 1) were administered every 3 weeks for up to 6 cycles with escalating doses of SS1P administered intravenously on days 1, 3, and 5 during cycles 1 and 2. Tumor response was evaluated every 6 weeks. RESULTS Twenty‐four patients received SS1P at 4 dose levels from 25 to 55 mcg/kg. Grade 3 fatigue was dose‐limiting in 1 patient at 55 mcg/kg. The MTD of SS1P was established as 45 mcg/kg. Other grade 3 toxicities associated with SS1P included hypoalbuminemia (21%), back pain (13%), and hypotension (8%). Of 20 evaluable patients, 12 (60%) had a partial response, 3 had stable disease, and 5 had progressive disease. Of 13 patients who received the MTD, 10 (77%) had a partial response, 1 had stable disease, and 2 had progressive disease. Objective radiologic responses were associated with significant decreases in serum mesothelin (P=.0030), megakaryocyte potentiating factor (P=.0005), and cancer antigen 125 (P < .0001). CONCLUSIONS SS1P given with pemetrexed and cisplatin is safe and well tolerated and exhibits significant antitumor activity in patients with unresectable, advanced pleural mesothelioma. Serum mesothelin, megakaryocyte potentiating factor, and cancer antigen 125 levels correlated with objective tumor responses. Cancer 2014;120:3311–3319. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

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Soluble Mesothelin, Megakaryocyte Potentiating Factor, and Osteopontin as Markers of Patient Response and Outcome in Mesothelioma

Abstract: SM and MPF levels were more closely associated with disease course than OPN and might prove useful in monitoring patient response in mesothelioma. Baseline OPN levels were an independent negative predictor of survival. These promising results require further validation.

Cited by 73 publications

References 36 publications

Effectiveness of mesothelin family proteins and osteopontin for malignant mesothelioma: Table 1–

Effectiveness of mesothelin family proteins and osteopontin for malignant mesothelioma: Table 1–

Serum mesothelin and other biomarkers: what have we learned in the last decade?

Phase 1 study of the antimesothelin immunotoxin SS1P in combination with pemetrexed and cisplatin for front‐line therapy of pleural mesothelioma and correlation of tumor response with serum mesothelin, megakaryocyte potentiating factor, and cancer antigen 125

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