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Targeted therapy drugs for mesothelioma attempt to kill cancer cells directly with minimal impact to healthy cells. Examples of targeted therapy drug types include vascular endothelial growth factor (VEGF) drugs, which suppress proteins needed for tumor cells to grow new blood vessels — essential to their survival.[1]
Since EGF receptors are highly expressed in MPM tumor cells, researchers hope that they can be used as a pathway for drugs to limit cancer growth and potentially kill of tumor cells. Unfortunately, a number of studies have been unable to uncover consistent anti-cancer activity from this group of drugs.[2]
Certain studies have uncovered promising results, however, making targeted therapy drugs a worthwhile avenue for further research into effective treatments for mesothelioma.
Common types of targeted therapy drugs include:
- NGR-hTNF
- Ganetespib
- Tazemetostat
- Onconase
NGR-hTNF (Zafiride)
NGR-hTNF is a substance being studied for its potential anti-cancer properties. It combines a peptide that readily binds to tumorous blood vessel tissues with a TNF (tumor necrosis factor) molecule that then damages these cells.[3]
Initial clinical trials reveal that NGR-hTNF was more effective at improving survivability compared with a placebo.[4] However, the poor prognosis of MPM patients meant that it became difficult for researchers to prevent adverse events — even if they were not directly related to interactions from the NGR-hTNF drug.[5]
At least one report, conducted by the European Medicines Agency, found that the drug trials did not pass the quality standards for clinical research to be sufficient to approve the therapy as a second-line treatment for mesothelioma patients.[6]
More research is needed to evaluate the efficacy of NGR-hTNF in human subjects and determine whether it should be recommended as a second or third-line treatment in mesothelioma patients.
Ganetespib
Ganetspib is a targeted therapy drug with potential applications for mesothelioma patients. The drug acts as an inhibitor of a crucial protein known as “heat shock protein 90,” or Hsp90 for short.[7] By attaching itself to Hsp90 and inhibiting its operation, Ganetspib can shut down other crucial cell mechanisms, potentially inhibiting the growth of tumor cells or even prompting cellular death.[8]
Some initial clinical trials evaluating the use of Ganetspib in combination with pemetrexed and platinum-based chemotherapy drugs have uncovered a favorable response rate.[9] Other research shows that the combination of the three is well-tolerated, with documentable anticancer activity.[10]
Clinical research of Ganetspib is ongoing, and more evaluation is needed to determine is level of effectiveness in patients with mesothelioma and other cancers.[11]
Tazemetostat
Tazemetostat is an orally administered anticancer drug that targets the EZH2 proteins, which are an essential component in the mutation of healthy cells into tumor cells and the proliferation of those tumor cells.[12] By targeting this protein, tazemetostat could potentially slow the growth and spread of tumors.
Early trials in patients with malignant mesothelioma show that tazemetostat holds promise for long-term disease control.[13] Further study is needed to evaluate its potential as a recommendable mesothelioma treatment.
Onconase
Onconase is a ribonuclease molecule that has been shown to have a cancer killing effect on tumor cells in vitro as well as in test animals. Research suggests that the molecule could also have the potential to enhance radiation or chemotherapy treatment.[14] The molecule is derived from the Northern leopard frog and modified to form a stable drug.[15]
In vitro tests exposing onconase to mesothelioma cancer tissues shows that it can suppress the growth of tumor cells and inhibit their ability to replicate.[16] In at least one clinical trial, which combined onconase with doxorubicin showed that survivability could be improved compared to doxorubicin alone.[17] More research is needed to evaluate the efficacy of the drug for use in patients with malignant mesothelioma.
[1] https://www.cancer.org/cancer/malignant-mesothelioma/treating/targeted-therapy.html
[2] https://www.medscape.com/viewarticle/760664_3
[3] https://www.cancer.gov/publications/dictionaries/cancer-terms/def/ngr-tnf
[4] https://ascopubs.org/doi/abs/10.1200/JCO.2018.36.15_suppl.8567
[5] https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30193-1/fulltext
[6] https://www.ema.europa.eu/en/documents/withdrawal-report/withdrawal-assessment-report-zafiride_en.pdf
[7] https://www.cancer.gov/publications/dictionaries/cancer-drug/def/ganetespib
[8] https://pubchem.ncbi.nlm.nih.gov/compound/Ganetespib
[9] https://seekingalpha.com/news/3392717-aldeyras-ganetespib-shows-positive-effect-mesothelioma-study-shares-ahead-5-percent-premarket
[10] https://www.jto.org/article/S1556-0864(18)31373-X/fulltext
[11] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4521669/
[12] https://pubchem.ncbi.nlm.nih.gov/compound/Tazemetostat
[13] https://ascopubs.org/doi/abs/10.1200/JCO.2018.36.15_suppl.8515
[14] https://www.ncbi.nlm.nih.gov/pubmed/18476793
[15] https://www.uniprot.org/uniprot/Q9I8V8
[16] https://www.nature.com/articles/onc2010643
[17] https://news.cancerconnect.com/mesothelioma/onconase-improves-survival-in-inoperable-mesothelioma-zV8eBmq340yOuyxn4lD-Jg/
