Targeting fibrosis has therapeutic benefits in mesothelioma. Most drugs have limited effects in difficult-to-treat cancers such as mesothelioma. Often this is because not enough of the drug can get into the tumor to generate an anti-tumor effect.
Fibrosis is a common element of mesothelioma. It causes the area around the cancer to stiffen. Fibrosis acts as a barrier, stopping drugs from getting into the cancer tumor. This limits the immune system’s ability to detect and access the tumor to kill it.
A new study is looking at how a family of proteins called lysyl oxidases can help solve this problem. These proteins are associated with fibrosis in many cancers, including mesothelioma. Oncologists targeting fibrosis and this protein family may improve mesothelioma treatment.
Fibrosis Blocks Treatment Drug Delivery and Immune Response
Immunotherapy and chemotherapy have limitations in the successful treatment of mesothelioma. When combined with fibrosis, mesothelioma treatments are further limited.
Fibrosis is the accumulation of collagen in the surrounding tumor tissues. It makes these tissues denser than healthy tissues. This affects drug delivery and immune cell infiltration.
Collagen production is controlled by a family of proteins called lysyl oxidases. Oncologists believe the pleural thickening in mesothelioma patients contains fibrotic tissue. This increases the surrounding tissue density and stiffness compared to healthy tissues.
Targeting Fibrosis for Therapeutic Benefits in Mesothelioma
Targeting fibrosis can prevent collagen formation, it may delay tumor growth in mesothelioma. A heightened presence of fibrosis, or collagen cells, often signals a poorer prognosis. Also, the over-production of collagen cells may be used as a diagnostic marker.
In other words, fibrosis acts as a red flag telling doctors that something is wrong. It also shows that the tumor may be amenable to therapeutic intervention.
There is strong rationale for targeting fibrosis as a therapeutic approach in mesothelioma.
Scientists have now confirmed that lysyl oxidases occur in primary malignant pleural mesothelioma. It occurs in both the tissues and cell lines. This finding was also confirmed in a similar Korean study.
Incorporating Fibrosis-Targeting Drugs in the Management of Mesothelioma
The fibrosis family of proteins is not controlled well in cancerous tissues. This often leads to solid tumor fibrosis and poor clinical outcomes for patients.
Drugs targeting fibrosis can be used to manage malignant pleural mesothelioma.
Dr. Steven Gray, a thoracic oncologist from St James’s Hospital, notes, “Given the significant roles of lysyl oxidases in both cancerous and fibrotic disease settings, coupled with the current development of small molecule inhibitors, it is our opinion that a strong rationale has emerged for the progression to clinical trials in mesothelioma.”
This is exciting news in the treatment of mesothelioma. There is strong evidence that lysyl oxidase cells are not controlled in mesothelioma. Lysyl oxidase blockers act as a mechanism of treatment to counter fibrosis.
These lysyl oxidase inhibitors could reduce mesothelioma patients’ fibrotic response. This would increase immune response, extend survival and increase the quality of life. It may even be possible to use lysyl oxidase inhibitors to prevent tumor metastasis.
Significant preclinical studies will need to test these promising results. But the current lysyl oxidase inhibitors are very encouraging.
Targeting fibrosis has potential therapeutic implications in the management of mesothelioma. Drugs that target fibrosis could be incorporated for the treatment of mesothelioma.
Perryman, L., & Gray, S. G. (2022). Fibrosis in Mesothelioma: Potential Role of Lysyl Oxidases. Cancers, 14(4), 981. https://doi.org/10.3390/cancers14040981