and Karl Reinhard Aigner3
(1)
Department of Surgery, The University of Sydney, Mosman, NSW, Australia
(2)
The Royal Prince Alfred and Sydney Hospitals, Mosman, NSW, Australia
(3)
Department of Surgical Oncology, Medias Clinic Surgical Oncology, Burghausen, Germany
In this chapter you will learn about:
Prevention
Improved cancer screening and diagnostic techniques
MRS (magnetic resonance spectroscopy)
Combined imaging using PET and CT or PET and MRI
Magnetic resonance-guided focused ultrasound surgery
Vaccines
Improved treatment agents
New agents
Therapeutic viruses
Targeted therapies
Improvements in radiotherapy
More effective integrated treatments with chemotherapy, radiotherapy and surgery
Prevention of metastases
Heat therapy
Other physical treatments – cryosurgery, electrolysis
Immunotherapy
Stem cell research
Genetic engineering and gene therapy
Studies in cell mediated anticancer activity
Molecular characterisation in future cancer treatment
Learning from “alternative” and “naturopathic” practices
Improved palliative care and supportive care
Hope for the future
The future for cancer sufferers is a mixture of hope and caution. Certainly there is much that can be done by application of present knowledge. There is also great expectation of future improvements in prevention, diagnosis and care. However, just as there will be great advances in management of cancer in the future, so too there will be new challenges. AIDS in Western countries is most prevalent in promiscuous male homosexuals and intravenous illicit drug users who share needles, but in some parts of Africa and Asia, it is widespread and increasing in both sexes. Affected people have increased susceptibility to infections and to developing malignant tumours. As yet, no cure is in sight.
People who have undergone organ transplantation and are dependent upon immune-suppressive drugs to prevent rejection of the transplanted organ also have an increased risk of developing a cancer, and the sexual revolution has exposed young women to an increased risk of developing cancer of the cervix. Lastly, it is quite unknown what potential other modern drugs, especially the illicit drugs, might have in regard to increasing the risk of some cancers. It took many years before the dangers of tobacco smoking became manifest.
24.1 Prevention (See Chap. 3)
Slim, fit, active people have a lower risk of several cancers
The most obvious measure in reducing the incidence of cancer is to avoid smoking. This has been known for years, but human nature being what it is, this precaution has been widely disregarded. Whilst ever there are large profits to be made from the sale of tobacco products, there will be resistance to the introduction of more severe statutory measures aimed at reducing smoking. Tobacco smoking is related to a greater incidence of cancers of the lung, mouth, throat, larynx, oesophagus, stomach, pancreas, large bowel, kidneys and bladder and even breast.
Another useful active measure is to encourage fair-skinned people to take greater protection against exposure to the sun and ultraviolet irradiation and especially for young people to avoid sunburn.
More attention can be paid to removal of pre-malignant conditions such as hyperkeratoses, leukoplakia, stomach and bowel polyps and papillomas and to avoid and prevent such infections as hepatitis and AIDS.
Some changes in lifestyle should be encouraged, including a reduction of animal fats and artificial additives and chemical preservatives and other contaminants in the diet. A greater intake of fibre, nuts, grains, fresh fruits and vegetables including legumes should also be encouraged as should moderation in the use of alcohol, although the possibility of some cancer protective value of a little red wine cannot be denied. There will continue to be advances based on epidemiological information such as a better understanding of protective qualities of high-fibre diets and apparent protective qualities of diets high in other possible protective agents such as phytoestrogens and lycopene.
General physical fitness with absence of obesity is desirable from every point of view. Slim, fit, active people have a lower risk of several cancers including lung, breast, colon and rectum, prostate and pancreas, as well as better ability to tolerate treatment programs.
Reduction of atmospheric pollutants, vigilant observation of protective industrial laws and protection against radioactive sources are also important preventive factors.
24.2 Improved Cancer Screening and Diagnostic Techniques (See Chap. 7)
Studies are being made in a number of laboratories to develop tumour markers that will detect cancers in their earliest stages.
Another measure of increasing importance is regular screening of people at special risk for certain kinds of cancer so that any early lesion may be treated before an advanced cancer develops. This may be most appropriate to detect early breast cancer, cancer of the cervix, cancer of the stomach in some communities and large bowel cancer. Screening for prostate cancer can often give a valuable guide but is not universally practised. It will be more widely accepted if a method can be developed for determining which prostate cancers are likely to become aggressive during the patient’s otherwise expected lifetime.
A newer technique of digital mammography is showing promise of improving the accuracy of diagnostic screening of breast cancer in women younger than 50.
It is anticipated that improved, more accurate and simpler screening measures for increasing numbers of different cancer types will become available. These may include simple blood screening tests for cancer antibodies or other tumour markers to indicate the presence of early cancer at a more curable stage and before symptoms have developed.
Improved diagnostic measures will also allow more certain and more accurate diagnosis at an earlier stage. Already improvements in CT scanning and other organ imaging techniques have made considerable progress and further advances are assured. Magnetic resonance imaging (MRI) has added to these improved diagnostic and imaging methods, and it is anticipated that positron emission tomography (PET) scanning might make an even greater impact than CT and MRI scanning within a few years (Chap. 7). PET gives information about the activity, composition and survival of tumour cells as well as detection of metastatic cells at an earlier stage than has been possible in the past.
Fine-needle aspiration cytology, frozen section techniques and other improved pathology techniques have allowed major progress in establishing early detection and the nature of early tumours. Improvements in the ability to examine body cavities with the use of flexible fibrescopes and endoscopes have allowed considerable progress in detecting and assessing early cancers in recent years. Such instruments and their application will undoubtedly continue to be improved.
Studies are being made in a number of laboratories to develop tumour markers that will detect cancers in their earliest stages. One such study with encouraging potential is a test for a molecule present when cells are abnormally dividing. Studies of bowel cancer are showing that this molecule is a possible indicator of the presence of a bowel cancer in its preclinical stages. A future screening test for bowel cancer may result. Studies are also being made in relation to other cancers including breast, bladder, cervix, mouth and lung.
24.2.1 MRS (Magnetic Resonance Spectroscopy)
MRS is an application of MRI. It is an evolving technology that has the potential to diagnose many tumours and characterise their metastatic potential. It is a non-invasive diagnostic test that uses strong magnetic fields to measure and analyse the chemical composition of human tissues.
New laboratory testing methods will also give information as to which treatment methods and which anti-cancer agents are likely to be of greatest benefit in treating each individual cancer; for example, a tumour cell scanning technique under study known as magnetic resonance scanning is investigating better methods of screening for and determining more specific anti-cancer chemotherapies for different cancers and trying to match each individual cancer with the agent or combination of agents to which it is most sensitive.
Experience with MRS of primary breast cancers indicates that it may also have a valuable application in other cancers. For example, it may be possible to predict the metastatic potential of melanoma by spectroscopic analysis of the primary tumour and to distinguish naevi from melanomas, thus better selecting patients for surgery.
24.2.2 Combined Imaging Using PET and CT or PET and MRI
Early imaging studies combining PET and CT or PET and MRI have shown prospects of demonstrating both functional and anatomical information of primary and metastatic cancers. Such combined imaging has considerable advantage in diagnosis and assessing response of cancers to treatment. Such techniques are sure to be further developed in the very near future.
24.2.3 Magnetic Resonance-Guided Focused Ultrasound Surgery
Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is a non-invasive technique that can coagulate tumours, both benign and malignant. It has been used in some clinical studies and has been shown, for example, to have potential as a non-invasive replacement for some open operative procedures such as lumpectomy of breast lumps. Undoubtedly it will become more widely used to remove other tumours in the future.
24.3 Vaccines
An effective vaccine traded as “Gardasil” (Merck) against the human papillomavirus has now been developed and successfully trailed for clinical use against cancer in humans. It is now used in several countries to vaccinate teenage girls. Progress is also being reported in developing vaccines against breast, colorectal, ovarian and kidney cancers and melanomas.
24.4 Improved Treatment Agents
Improved treatment with more effective and more specific anti-cancer drugs is proceeding, and there is constant progress in how best to use anti-cancer drugs in appropriate combinations and treatment schedules. Newer and more effective anti-cancer agents like the taxanes (derived from a plant) are adding to the range of available anti-cancer drugs, and many drugs are being made safer and more effective by increasing availability of agents that protect the bone marrow and other body tissues.
Solving many of the problems of bone marrow transplantation has also allowed stronger and more effective anti-cancer treatment to be given with improved safety. It is anticipated that heavy-dose chemotherapy with life-saving bone marrow transplantation may be used effectively in treating patients with more types of widespread cancer. At present, only limited numbers of tumour types, mostly lymphomas and leukaemias, can be effectively treated this way with relative safety.
Another class of agents, Cox–2 inhibitors, is being tested in both prevention and clinical trials. Epidemiological studies have shown that people who regularly take nonsteroidal anti-inflammatory drugs, such as aspirin, for arthritis, have lower rates of colorectal polyps and colorectal cancers. These block certain enzymes (cyclooxygenase enzymes) that are produced in the body when there is inflammation and are also produced by precancerous tissues. Inhibition of Cox-2 enzymes may help treat and prevent cancer. Clinical trials of new Cox-2 inhibitors (one is called celecoxib) in cancer prevention and cancer treatment are under study.
24.5 Self-Rescuing Concept (SRC)
S-1 is an active oral fluorouracil antitumour drug, which is called a “self-rescuing” drug. This is the first of a new concept of combining an anti-cancer agent (5-FU) with a protective or self-regulating agent to give dual actions that are enhancement of pharmacological actions of 5-FU and reduction of its adverse reactions by making use of the biochemical and enzymological properties of 5-FU in combination with FT, which is gradually converted to 5-FU in the body, with a 5-FU’s adverse reaction reducing substance.
It seems that the combined regimen of S-1 with other anti-cancer agents and with other therapeutic modalities will contribute to the routine medical practice of cancer treatment in the future.
S-1-based combination therapies with other promising drugs like cisplatin, irinotecan and taxanes are expected to yield good results. Above all, S-1 plus CDDO therapy showed a high efficacy and is expected to become a standard therapy for advanced gastric cancer.
24.6 New Agents
A whole range of new anti-cancer agents is presently undergoing trials in cancer treatment, and some are proving to be very effective. Some under study have been mentioned in this book in treating different cancers (Chaps. 8 and 19). The most significant of these new agents are gemcitabine, vinorelbine, topoisomerase I inhibitors (topotecan, irinotecan), liposomal anthracyclines, new fluoropyrimidines and tyrosine kinase inhibitors, but as progress is made, more agents will be added to this list and some older agents will no longer be used.
24.7 Therapeutic Viruses
A new approach in anti-cancer treatment is to find a virus that will specifically damage cancer cells without damaging normal cells. In some laboratories, genetically engineered anti-cancer viruses are being designed. Present laboratory studies in relation to breast cancer cells have been encouraging although the anti-cancer potency has been shown to become less effective with prolonged use. An adenovirus (OnyxO15) has been developed which specifically kills head and neck cancer cells with p53 mutations, though not as simply as originally thought. A variant of this has been licensed in China, though its approval and use remains controversial. At the time of writing, safety and effectiveness in clinical studies has rarely yet been demonstrated.
24.8 Targeted Therapies
Recently, a new avenue of cancer chemotherapy began to show promise with the discovery of an antagonist to the enzyme involved in myeloid leukaemia, tyrosine kinase, STI571 (Gleevec or Glivec). The discovery of this agent has stimulated further research to discover more inhibitors of possible enzymes involved in production of other cancers (see Sect. 19.4). Future enzyme treatment of prostate cancer and certain gastrointestinal cancers appears promising.
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