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Mesothelioma : Current Status

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What is Mesothelioma?

Mesothelioma is asbestos-related cancer. The linings of the lungs and abdomen are the most usually affected. The usual life expectancy following diagnosis is 18–31 months, but the prognosis may improve with treatment. Chest pain, shortness of breath, and overall weariness are all possible symptoms. It’s a cancer of the mesothelium, which is a membrane that lines the inside of body cavities like the belly and chest. Mesothelioma illness starts in the chest cavity in three out of every four patients. Mesothelioma can start in the abdominal cavity or the area around the heart.

Malignant cells from the mesothelium can penetrate and damage neighboring tissues regardless of where they come from. Cancer cells can also move to other places of the body, known as metastasis. The disease is often advanced by the time mesothelioma is detected. The 5-year survival rate is in the range of 5% to 10%. Respiratory failure or pneumonia are the most common causes of death in patients with lung mesothelioma. When a tumor grows through the diaphragm, a muscle that separates the chest and abdominal cavities, some patients experience a small-bowel obstruction. When the tumor invades the pericardium (a thin sac that surrounds the heart) and the heart itself, a lesser number of people die from heart issues.

Common Symptoms of Mesothelioma

  • Chest pain or abdominal pain

  • Shortness of breath

  • Fluid buildup

  • Fatigue

  • Fever and night sweats

  • Weight loss

Asbestos

The most common cause of mesothelioma is asbestos exposure. Asbestos is carcinogenic in all forms. At least 90% of all cases of mesothelioma are caused by asbestos exposure.

Asbestos fibers can become implanted in the lungs, stomach cavity, or cardiac lining when inhaled or swallowed. When the fibers become lodged, they produce inflammation and scarring, which can develop into mesothelioma tumors. Other asbestos-related disorders, such as asbestosis, can be contracted by inhaling the fibers.

Asbestos fibers cause both indirect and direct DNA damage, in addition to inflammation and scarring.

Direct Injuries

  • Asbestos causes cell division to be disrupted.

  • This interference has the potential to harm cells.

  • Cancerous mutations may occur as a result of cellular alterations.

Indirect Injury

  • Asbestos can induce immune cells to emit harmful substances, causing inflammation and fibrosis in the lungs.

  • This inflammation can lead to DNA damage and cancer over time.

Types of Mesothelioma

The type of mesothelioma that develops is determined by the location of the lodged asbestos fibers and damaged DNA.

  • The lining of the abdomen is affected by peritoneal mesothelioma.

  • Pleural mesothelioma is cancer that develops in the lungs and chest wall lining.

  • The lining of the heart develops pericardial mesothelioma.

  • Patients with mesothelioma generally don’t show symptoms for 10 to 50 years after being exposed to asbestos.

What does current research say?

None of the ‘traditional’ diagnostic biomarkers evaluated in biological fluids, such as cytokeratins and cell surface antigens, can distinguish MPM patients from those with other malignancies or nonmalignant disorders. The most promising recent biomarkers appear to be osteopontin, soluble mesothelin, and megakaryocyte potentiating factor (MPF), however, they are still limited. Both soluble mesothelin and MPF have little sensitivity for detecting non-epithelial subtypes, while osteopontin has no specificity for mesothelioma.

In 2020, the global number of new cases of malignant mesothelioma is expected to reach 30,870, representing 0.2 percent of all new malignant tumors, while the number of fatalities is expected to reach 26,278, accounting for 0.3 percent of all malignant tumor deaths.

Great progress has been made in immunotherapy against many cancers thanks to the use of ICIs (Immune checkpoint inhibitors, ICIs). Immunotherapy seeks to engage the immune system so that tumor-specific immune responses can be triggered. Currently, three types of ICIs, including programmed death-1 (PD-1), PD-1 ligand-1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), can be used to suppress the immunosuppressive substances listed below (CTLA-4). Positive findings were first observed in a recent Phase III trial integrating aCTLA-4 (ipilimumab) and aPD-1 (nivolumab) among treatment-naive MPM subjects (specifically, Checkmate-743).

The US FDA authorized Opdivo (nivolumab) in conjunction with Yervoy (ipilimumab, Bristol-Myers Squibb Company) as the first-line treatment for unresectable adult MPM patients on October 2nd, 2020. It gives me great pleasure to announce that this is the first drug approved by the FDA for systemic therapy of MPM in 16 years, as well as the second kind of drug approved by the FDA for the systematic treatment of MPM in its history, following the approval of pemetrexed combined with cisplatin in 2004.

MPM was a possible attractive candidate for immunotherapy, according to a basic study on the immunosuppressive tumor microenvironment (TME) of MPM. It is suggested that ICIs be used to achieve several promising outcomes. Immunotherapy has shown to be effective in MPM patients in other experimental studies. DREAM was a Phase II multicenter, single-arm, open-label trial that was the first to combine the PD-L1 inhibitor durvalumab with platinum-based chemotherapy in the first-line treatment of MPM. Durvalumab was sustained for a maximum of 12 months in 31 (57 percent; 95 percent CI 44–70) of 54 patients who were alive and progression-free at 6 months. Chemotherapy combined with immunotherapy improves the 6-month progression-free survival rate and ORR (objective response rate) when compared to chemotherapy alone, and the adverse effects are manageable.

Sources and references : https://www.mesothelioma.com

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