Chinese researchers observed that DFMO (a-difluoromethylornithine) treatment could significantly restrict the tumor growth in resectable malignant pleural mesothelioma (MPM) patients who have undergone U.S. FDA approved chemotherapeutic treatment. DFMO treatment reduces the production of tumor-enhancing polyamines.
The unresectable tumor cannot be removed with the surgery, whereas resectable tumors can get removed with surgical treatment.
Researchers from The University of Hong Kong published studied a potential adjuvant treatment for resected malignant pleural mesothelioma, treated at an early stage.
The Journal of Clinical Oncology published this research on May 26, 2019.
Importance of Adjuvant Therapy in Malignant Pleural Mesothelioma
The U.S Food and Drug Administration-FDA has approved the combination of cisplatin and pemetrexed as a chemotherapeutic treatment for malignant pleural mesothelioma. And recently, on May 23, 2019, FDA has approved NovoTTF-100L plus chemotherapy to treat unresectable mesothelioma.
Although resectable tumors can get surgically treated, still there are strong chances of tumor growth after the surgery. That's why efficient adjuvant therapeutic options are urgently required to restrict the regeneration of tumor growth in malignant pleural mesothelioma patients.
Reason for Tumor Growth After Chemotherapy
Through initial experimental data, the researchers have observed that the expression of enzyme ornithine decarboxylase (ODC) increased in the mesothelioma tumor samples.
The primary function of the ODC enzyme is the production of polyamines, and these polyamines function for the growth and stabilization of tumor cells.
Therefore, it is necessary to introduce an anti-ODC substance in the body after chemotherapy to restrict the production of polyamines and thus halt tumor formation.
The Decrease in the Tumor Growth with DFMO Treatment
DFMO functions as the DFMO inhibitor. The researchers studied the effect of DFMO treatment against metastatic tumors and as adjuvant therapy.
Upon testing these effects, malignant pleural mesothelioma tumor was grafted in the animal model, mice.
To check the role of DFMO as adjuvant therapy, the mice fed with DFMO containing water and a substantial amount of tumor cells after seven days. After reaching the tumor growth of more than 600mm3, the researchers observed,
"In an adjuvant therapy setting, DFMO suppressed tumor growth and increased median survival in both 211H and H226 xenografts."
DFMO treatment on metastatic mesothelioma cells also showed a decrease in tumor growth.
The researchers wrote,
"In a therapeutic setting, DFMO also suppressed tumor growth in both xenografts with similar mechanisms."
Alterations in the Polyamines Level
The reduction in tumor growth is because of the decrease in the production of polyamine. DFMO reduced the growth of the ODC enzyme, and thereby, the associated increase in the polyamine level reduced. Dr. James C M HO, one of the lead scientists of the study, wrote,
"Upon DFMO treatment, a decrease in spermidine level, increase in nitrotyrosine content, and activation of apoptosis were observed in both xenografts."
Researchers observed tumor cell death (apoptosis) as a consequence of the decrease in the spermidine (polyamine) level and increased in the nitrotyrosine level.
In adjuvant therapy, DFMO significantly induced tumor-suppressing hormones. Simultaneously, it inhibited tumor-enhancing pathways. The researchers observed that,
"In addition, an increase in nitrosocysteine level, intratumoral IL-6, keratinocyte chemoattractant, and TNFα, DNA lesions and inhibition of Akt/mTOR pathway were induced by DFMO in H226 xenografts, which may explain higher potency of DFMO in these xenografts."
DFMO Treatment as Potential Adjuvant Therapeutic Option in Malignant Pleural Mesothelioma
The researchers concluded that further research in this regard could open doors for complete removal of mesothelioma tumor without worrying about its regeneration.
The lead author, Dr. James wrote in the paper,
"DFMO may have a potential role as adjuvant therapy in MPM, especially epithelioid mesothelioma."