New targets for diagnosis and treatment

This page presents information on diagnostic and predictive markers and targeted cancer therapies.

Our increasing understanding of the genes involved in the development of cancer is beginning to translate into new treatments, better methods of diagnosis and the potential to predict the outcome of therapy.

Diagnostic and predictive markers

Specific alterations in genes and the proteins they code for have been identified in many types of cancer. Some of these alterations hold promise for use as molecular markers in diagnosis and early detection, or for monitoring disease progression and response to treatment. 1

Alongside this, scientists are using the latest microarray technologies to reveal genetic variations between cancers of the same type in different individuals. The genetic signature of a person’s tumour may influence the outcome of radiotherapy, drug or hormone treatment. Increasingly, this information will be translated into the clinic, allowing doctors to tailor treatment to the individual patient.

Targeted cancer therapies

The advances made in understanding the genetic and molecular basis of cancer over the last few decades are enabling the rational design and development of new types of cancer therapies. Some aim to exploit the molecular differences between cancer cells and normal cells. Others seek to undermine the mechanisms used by cancer cells to evade the lethal effects of other treatments. These novel, targeted approaches should both increase the efficacy of treatment and reduce the side effects experienced by patients.

The most well established of these new therapies are monoclonal antibodies and small-molecule tyrosine kinase inhibitors. Many of these interrupt the positive growth signals transmitted by the protein products of oncogenes.

A number of monoclonal antibodies and tyrosine kinase inhibitors are currently in clinical use or in development ( Table 5.1). 2, 3

Some of these therapies have had dramatic effects on survival. For example, Glivec® (imatinib mesylate) is a tyrosine kinase inhibitor that prevents activation of the Bcr-Abl protein, and, as a result, inhibits cell proliferation and promotes apoptosis. 4

In England and Wales, Glivec® is now recommended as the first-line treatment for adults with chronic phase BCR-ABL-positive CML. 5 The drug has also shown activity in chemoresistant gastrointestinal stromal tumours, 6 where it targets the Kit receptor, and is recommended for first-line treatment of people with these tumours in England and Wales. 7

Recently, the monoclonal antibody therapy Herceptin® (trastuzumab), which targets the cell surface HER2 growth factor receptor (also known as c-ErbB2), has received a lot of press coverage. HER2 is overexpressed in around a quarter of all breast cancers. Herceptin® has been recommended for treating metastatic breast cancer for some time, where, in combination with chemotherapy, it improves patient survival 63 8 whilst maintaining quality of life. 9

In 2005 and 2006 the drug was approved in Northern Ireland, Scotland, England and Wales for use as adjuvant therapy in early stage breast cancer. 10, 11

Table 5.1: Examples of targeted cancer therapies

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Since most of these targeted therapies tend to affect a single pathway in the cancer cell, combinations of agents that target several pathways may prove to be more effective than any single agent. A multi-therapy approach could also help overcome resistance to single agent treatment. 3

Many other types of therapy designed to exploit the subtle differences between cancer and normal cells are being developed. These include gene therapy, 12 oncolytic viruses 13 and antibody-directed drugs and radionuclides. reviewed in 14, 15

 
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References for new targets for diagnosis and treatment

  1. Sidransky, D., Emerging molecular markers of cancer. Nat Rev Cancer, 2002. 2(3): p. 210-9
  2. Imai, K. and A. Takaoka, Comparing antibody and small-molecule therapies for cancer. Nat Rev Cancer, 2006. 6(9): p. 714-27
  3. Dancey, J.E. and H.X. Chen, Strategies for optimizing combinations of molecularly targeted anticancer agents. Nat Rev Drug Discov, 2006. 5(8): p. 649-59
  4. Inokuchi, K., Chronic myelogenous leukemia: from molecular biology to clinical aspects and novel targeted therapies. J Nippon Med Sch, 2006. 73(4): p. 178-92
  5. NICE Guidance - Leukaemia (Chronic Myeloid).
  6. Joensuu, H., et al., Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl J Med, 2001. 344(14): p. 1052-6
  7. NICE Guidance - Gastro-Intestinal Stromal Tumours.
  8. Slamon, D.J., et al., Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med, 2001. 344(11): p. 783-92
  9. Osoba, D., et al., Effects on quality of life of combined trastuzumab and chemotherapy in women with metastatic breast cancer. J Clin Oncol, 2002. 20(14): p. 3106-13
  10. NICE Guidance - Breast Cancer
  11. Scottish Medicines. 2008
  12. Cross, D. and J.K. Burmester, Gene therapy for cancer treatment: past, present and future. Clin Med Res, 2006. 4(3): p. 218-27
  13. Chernajovsky, Y., L. Layward, and N. Lemoine, Fighting cancer with oncolytic viruses. Bmj, 2006. 332(7534): p. 170-2
  14. Schrama, D., R.A. Reisfeld, and J.C. Becker, Antibody targeted drugs as cancer therapeutics. Nat Rev Drug Discov, 2006. 5(2): p. 147-59
  15. Sharkey, R.M. and D.M. Goldenberg, Targeted therapy of cancer: new prospects for antibodies and immunoconjugates. CA Cancer J Clin, 2006. 56(4): p. 226-43