Lung cancer and mesothelioma are both devastating diseases that are often resistant to effective treatment methods. This is especially true of mesothelioma because all forms of the disease, including the most common forms of pleural mesothelioma and peritoneal mesothelioma, are without a cure, but it is also true of many variations of lung cancer as well, or of lung cancer that is only diagnosed in the advanced stages. Surgery, chemotherapy and radiation therapy remain the major modalities of treatment, but there is also an active research community investigating cellular, molecular, and gene therapies and some of the research in those fields is quite promising. As an example of these latter research fields, doctors from Australia and South Africa have recently released a report on the molecular genetics and mechanisms of apoptosis in cancers of the lung and the pleura.

Overview of the Study

Even as the overall deaths from cancer are going down in much of the industrialized world, lung cancer still accounts for the single highest percentage of deaths as compared to any other single form of cancer. Most of these deaths can be traced back to smoking tobacco or being exposed to second-hand smoke, but there are other causes of it as well: asbestos, chromates, nickel, radioactive materials and silica dust being some examples of the alternative causes. Mesothelioma is a relatively rare disease in the general public, but among asbestos workers it is not a rare disease at all. It is extraordinarily difficult to treat and no single cure exists for people who’ve been diagnosed with it. Because of these realities, research into cancer treatments probably accounts for the greatest share of medical research being done internationally.

Some of this previous research into carcinogenicity has shown a number of important cellular and molecular mechanisms at work in the development of cancer, including chromosomal aberrations and the inhibition of both tumor suppressor genes and apoptosis because of these aberrations.

Researchers have identified mutations in the tumor suppressor genes TP53 and RB as causative of cancers in the lung and pleura. The mutations lead to an inhibition of these genes’ ability to suppress tumor growth, which means that one of the body’s fundamental processes that regulates a healthy system is undermined by a genetic mutation. Another important cellular mechanism that is compromised in the development of these cancers is inhibition of apoptosis in affected cells. Apoptosis is the process by which damaged cells remove themselves from the replication cycle. In effect, it is a function of the cell to kill itself if it doesn’t meet the necessary structural components of a healthy cell. When apoptosis is inhibited, malignant cells that should have been removed from the cell cycle are not, in fact, removed, so the damaged cells continue to replicate, which puts the entire system at risk for the development of a cancer.

Therapeutic Targets

Researchers have begun to develop strategies to combat these carcinogenic activities. One of the most promising is developing chemotherapy agents that directly target the anti-apoptotic feature expressed in malignant tumors. Another strategy being researched is re-sensitizing cancerous cells to the signaling methods and molecular pathways the body uses to trigger apoptosis in affected cells.

One of the most difficult aspects of cancer research is the very nature of cancer itself: it is less a single disease than it is a family of diseases that targets specific cells in very certain ways. For example, we speak of “lung cancer” as a single disease, but in fact there are multiple forms that lung cancer can take: adenocarcinoma, non-small cell lung cancer, squamous cell carcinoma, etc., etc. The same is true for mesothelioma. There are the primary origin sites of mesothelioma, such as pleural mesothelioma or peritoneal mesothelioma, and there are also the histological subtypes of the disease: epitheloid, sarcomatous and bi-phasic. Because the individual expressions of these cancers take forms particular to certain parts of the body, research needs to account for multiple mechanisms of action in any single disease family.

The authors provide an overview of a number of possible treatment targets in addition to the ones that were discussed here. Gene therapy and the development of stem cell therapy also offer great promise for the treatment of a variety of cancers, including lung cancer and mesothelioma.

Conclusion

There is much to be excited about in cancer research these days, but the reality is that mesothelioma and lung cancer continue to take lives. Research into new modalities of treatment is always welcome and as we progress farther in our understanding of the underlying mechanisms involved, doctors and patients alike look to the day when a cure is discovered.

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