Medical advancements in treating malignant Mesothelioma involve decisive approaches and different clinical trial phases with monitoring each and every stage. It involves lot of time and effort to put forth something as a solution. The breakthroughs in mesothelioma clinical trials are moving towards conventional treatment approaches to make patients live better. That’s what all the medical advancements are about, to make people look for something to hope. When it comes to mesothelioma, Survival rates can be increased but we are still failing in finding complete cure for mesothelioma. The aggressive nature of Mesothelioma is very challenging to treat and the emerging trends to treat Malignant Pleural Mesothelioma (MPM) / Maligant Mesothlima Cancer are still being explored in every way possible to bring a feasible solution.
The Latest Developments & New Opportunities In The Treatment Of Mesothelioma
The Malignant Pleural Mesothelioma(MPM) is male-predominant disease with more than 75% of the cause is being occupational and environmental exposure to asbestos. Once diagnosed, the survival rate is limited to 12 to 18 months. The poor prognosis nature of mesothelioma is a biggest drawback. The reason is due to lack of reliable tools for proper screening and systematic therapy approach. Surgery can be attempted in only very few cases that too depending on their stage at which the MPM is diagnosed.
1.The Need for Good Diagnostic Mesothelioma Biomarkers
Many labs, top cancer researches and clinical research facilities are prompting further research towards finding a novel, more sensitive and accurate biomarkers. With biomarkers, you can become more aware of early detection, treatment effectiveness and risk factors involved with mesothelioma cancer. In case of subjects with high levels of asbestos exposure, good biomarker for early detection of mesothelioma is a must.
Mesothelin is being extensively used as a potential biomarker for malignant mesothelioma. The ecto-NOX disulfide-thiol exchanger 2 as a potential early detection marker for mesothelioma is showing improved results. Other effective biomarkers like Osteopontin, cancer antigen 125, hyaluronic acid, fibulin 3, and high mobility group box 1 (HMGB1) are being studied in mesothelioma. They tend to lack specificity but they are little better in having some value in prognostication. Overall, Biomarkers for early detection of MPM is a good step towards mesothelioma treatment advancements and all researches are focusing on it.
2. Immunotherapy Treatment for Mesothelioma
It has been known that the Malignant Mesothelioma cancer can be sensitive to immunotherapy, body’s immune system and some immunotherapies are being tested with it. Immunotherapy is being considered as the future line of treatments for mesothelioma. An immunotherapy drug follows an entirely different class of treatment strategies targeting the body’s core immune system to combat mesothelioma malignancy. Immunotherapy results in fewer and less-severe side effects when compared with surgery and chemo. Mesothelioma Treatment researches involve using immunotherapy to go after the cancer cells , to reveal them to the body’s core immune system which can fight and destroy outsiders naturally.
Keytruda and Opdivo are notable immunotherapy drugs used in treatment of mesothelioma. They are more like immunotherapy check-point inhibitors. Keytruda works by blocking the interaction of PD-L1 proteins on cancer cells with PD-1 proteins on the body’s immune system cells. Malignant mesothelioma tends to use PD-L1 protein as a mask to hide from body’s immune system and Keytruda works against it.
Do Tecentriq (Atezolizumab) Treat Malignant Mesothelioma Effectively
Tecentriq immunotherapy drug is found to show better results than other immunotherapy mesothelioma drugs like Keytruda and Opdivo. Tecentriq is designed to target a specific protein that stops the body’s immune system from recognizing the cancer cells. By negating the protein, the immune system becomes more aware of the cancer presence and can work effectively in recognizing and destroying the tumor cells.Tecentriq is the first FDA-Approved anti- PDL1 cancer immunotherapy drug for mesothelioma.
How Tecentriq Works Against Malignant Pleural Mesothelioma?
In general a Tecentriq is given after other cancer medicines have been put to use and with no success as result. Tecentriq is often used in the multi-modal treatment of mesothelioma combined with other treatment regimen. Tecentriq is a Monoclonal Antibody that works by affecting the body’s immune system. It preps the immune system by strengthening it and to become aware cancer cell presence and fights against it. According to Seattle Cancer Care Alliance (SCCA), the Monoclonal Antibodies such as Tecentriq may interfere with the ability of tumor cells to grow and spread. Giving Tecentriq with other drugs like pemetrexed disodium and cisplatin helps to stop the growth of tumor cells wither by killing the cells or stopping them from dividing or stops them from spreading. Administering Tecentriq after surgery may have kill remaining tumor cells.
Antibodies Blocking Immune Checkpoints Studies And Tests
The treatment advancements for Mesothelioma includes studies conducted over potent Anti-bodies that blocks the immune checkpoints for use in immunotherapy for MPM. Antibodies blocking immune checkpoints functions as negative regulators of T-Cell function. The use of CTLA4 (cytotoxic T-lymphocyte–associated antigen 4) and studies assessing the possibility of combinations of PD-1 or PD-L1targeted therapies with CTLA4antibodies are going on.
Overall, preliminary data on studies with PL-1 (proteins on immune system) and PD-L1 (proteins of mesothelioma cancer cells) targeting monoclonal antibodies (like the Tecentriq) in Malignant Pleural Mesothelioma suggests that single-agent immunotherapy might show some benefits in this cancer disease. Additional studies are going on over mesothelioma treatments in this area.
3. Mesothelioma Treatment In The Line Of Stem Cells
Stem cells are small population of cells within each tumor that has the properties of self-renewal and high ability to resist drugs, chemo and radiation. These Drug-Resistant stem cells provide different strategies and approaches to take up research work. Studying them can help improve the efficacy of cytotoxic drugs and can identify the reason behind resistance of MPM to conventional cytotoxic drugs.
Several stem-cell related research for mesothelioma treatments are going on as we speak. The Wnt, Hippo and Sonic Hedgehog are active areas of drug development in the line of stem-cells which are showing positive preclinical results in mesothelioma treatment.
According to ‘Anticancer Res. 2007; 4239-4242’, In Mesothelioma, combining Cisplatin with Wnt Pathway inhibitors in vitro improves the efficacy of standard chemotherapy and induces synergistic cell cycle arrest and colony formation.
Another area of interest in mesothelioma treatment advancements and trends is into Sonic Hedgehog pathway, controlling the progenitor cell migration, differentiation and proliferation. There are preclinical developments that suppresses the mesothelioma cell growth using cell inhibitors and in stem-cell pathway areas.
4.Using Virotherapy for Malignant Pleural Mesothelioma – Concept of using Viruses for Cancer Treatment and Therapy
Advancements in genetic engineering have pioneered the use of potent viruses against cancer causing tumor cells in the body. Viroimmunotherapy is a new frontier in mesothelioma treatment approach. Viruses are being used to therapeutically change the infected tumor cells by gene transfer/gene therapy. Recent advancements in gene therapy and genetic engineering have helped design therapeutic viruses with enhanced tumor cell-specific targeting. For MPM, the Virotherapy is still in experimental treatment strategy and it needs more results and data to back it up. Clinical studies investigating the intrapleural administration of modified virus strains vaccines for MPM are being carried on. Combinatorial approaches like using immune checkpoint inhibitors, chemo and enhancing the effects of the viruses on anti-tumor immunity are being researched now. Using Virotherapy for treatment of mesothelioma is getting closer day by day towards positive results.
5.Approach Of Using Angiogenesis Inhibitors For Mesothelioma Cancer Treatment
Angiogenesis is the formation of new blood vessels to carry oxygen and nutrients. The process is a normal part of healing done by our body. But the same becomes a danger in case of cancer as tumor cells use these blood vessels to bring nutrients and oxygen for their growth. Angiogenesis inhibitors aka Antiangiogenic drugs blocks angiogenesis. Antiangiogenic drug works by blocking nutrients and oxygen to the tumor which eventually starves them out. Using this technique in the treatment of mesothelioma is being conducted with different phases of trials while few options are being included in the ‘National Comprehensive Cancer Network Guidelines’ to proceed with further line of treatment. Large randomized clinical trials and results might not be successful but still the progress and correction are being studied.
6.Radiation Therapy For Mesothelioma
Radiation is an important stage in treating any form of cancer. Mesothelioma is shown to be sensitive towards radiation in in-vitro studies conducted. Usually it is done in three different stages for MPM.Palliative Radiation is used for treatment of pain or an area at risk of compression such as esophagus or in case of related to heart area like superior vena cava. We have prophylactic radiation after large-bore pleural biopsy. The other method involves radically in the form of high dose hemithoracic radiation to improve survival factors. Among them the prophylactic radiation is of non-beneficial and has been not used. In other case, the palliative radiation trials over patients have found to improve pain situation. But the main importance is towards the hemithoracic radiation and the possibility of using it with multimodal approach. Using hemithoracic radiation as part of multimodality approach are being performed in experienced centers in single-arm clinical trials. The trials are shown to give positive approaches in terms of safety. Further studies are currently going on to evaluate the benefits of these multimodal therapeutic approaches for treating mesothelioma. The optimal radiation regimen is also being researched upon during clinical trials.
7.Adjuvant Therapies For Mesothelioma
Adjuvant therapy is another approach towards exploring new angle in mesothelioma treatment. Neo-adjuvant therapies are given to patients before the main treatment to help reduce the size of the tumor or kill the cancer cells that have spread. Adjuvant therapies are given after primary treatment to destroy remaining cancer cells. There are currently many trials going on in to Neo-Adjuvant settings in which immunotherapies are being used and certain drugs given in Neo-adjuvant settings tend to contribute to tumor shrinkage while maintaining low toxicity. But during and after surgery, there may be a drawback of microscopic disease. To eliminate that risk, certain drugs are administered in the adjuvant maintenance settings. The adjuvant therapy settings with MPM are still undergoing different clinical trials and multimodality approaches to treat mesothelioma. The possibility of using Antiangiogenic agent with Neo-Adjuvant chemotherapy setting with low complication rate is found feasible. The main purpose of Adjuvant and Neo-Adjuvant settings is in opening up significant opportunities to conduct translational research to get to know more about mesothelioma.
8.Different Approaches And Emerging Treatment Advancements In Mesothelioma
According to ‘Journal of Thoracic Oncology Vol. 13No 9: 1269-1283”, some of the advanced treatment approaches for mesothelioma that are still under Clinical Trials include:
- Targeted Therapy with Mesothelin
- Immune Check-Point Blockade
- Anti-Angiogenesis Therapies
- Dendritic cell based vaccines
- Viral therapies that include intrapleural administration
- Arginine Deprivation Therapy
The above methods and techniques are under preclinical trials and few are in patient trials carried on the hope of finding a better solution.
Future Approaches Towards Mesothelioma
When it comes to treatment of mesothelioma cancer, the advancements, studies, researches and clinical trials are being done every day with the perspective of bringing a solution and to think outside the box to find the cure. It involves more effort, funding and time which is why it takes years to perfect the proper clinical treatment advancement method to even begin a clinical trial. Although there hasn’t been very significant improvement in mesothelioma treatment, the route towards better understanding the complex nature of mesothelioma is coming closer than years back. Good knowledge of MPM’s complex biology structure will helps us move forwards and gain a solid ground about this disease. Science continues to grow everyday which gives us hope. The treatment angle for mesothelioma is shifting towards more outside thinking and we hope there comes a day in the not-so-near future to find a perfect cancer cure.