TARGETED THERAPY: A SMARTER CANCER THERAPY

Cancer therapy is getting smarter, with new drugs that act specifically against cancer cells. Targeted therapy is a new type of cancer treatment that uses drugs or other substances to identify and attack cancer cells while doing little damage to normal cells.

Targeted therapies are a major focus of cancer research today. Many future advances against cancer will likely come from this field. Dr T.Raja, Consultant Oncologist, Apollo Specialty Cancer Hospitals discusses this major new advance in Cancer Chemotherapy

Cellular Changes during Cancer

Normally, cells grow and divide to form new cells as the body needs them. Sometimes this orderly process goes wrong. New cells form when the body does not need them, and old cells do not die when they should. These extra cells can form a mass of tissue called a growth or tumor.

The cells in malignant (cancerous) tumors are abnormal and divide without control or order. They can invade and damage nearby tissues and organs. Also, cancer cells can break away from a malignant tumor and spread to other parts of the body.

Alterations in two types of genes can contribute to the cancer process. Proto-oncogenes are normal genes that are involved in cell growth and division. Changes in these genes lead to the development of oncogenes, which can promote or allow excessive and continuous cell growth and division. Tumour Suppressor genes are normal genes that slow down cell growth and division. When a tumor suppressor gene does not work properly, cells may be unable to stop growing and dividing, which leads to tumor growth.

These changes happening in the genes can lead to the production of abnormal proteins. Cancer develops when abnormal proteins inside a cell cause it to reproduce excessively and allow that cell to live longer than normal cells.

Targeted therapy

Targeted therapy is a general term that refers to a medication or drug that targets a specific pathway in the growth and development of a tumor. Targeted therapy agents work by targeting specific PROTEINS and processes that are limited primarily to cancer cells or that are much more prevalent in cancer cells. Inhibition of these processes prevents cancer cell growth and division.

Mode of action of Targeted Therapies

Targeted cancer therapies interfere with cancer cell growth and division in different ways and at various points during the development, growth, and spread of cancer.

Many of these therapies focus on proteins that are involved in the signaling process. By blocking the signals that tell cancer cells to grow and divide uncontrollably, targeted cancer therapies can help to stop the growth and division of cancer cells.

Types of Targeted Therapy:

I) Tyrosine kinase receptor inhibitors

A tyrosine kinase receptor is a molecular structure or site on the surface of a cell that binds with substances such as hormones, antigens, drugs, or neurotransmitters. When it binds with one of these triggering substances, the receptor performs a chemical reaction, which in turn triggers a series of reactions inside the cell. Examples of these drugs would be Gefitinib, Erlotinib,Trastuzunab etc

II) Angiogenesis inhibitors

Tumor cells, like normal cells, need an adequate blood supply in order to perform vital cellular functions. This new blood vessel formation is called angiogenesis and the proteins that trigger this process are called proangiogenic factors.

The main proangiogenic factor is VEGF, which stands for vascular endothelial growth factor. In essence, by secreting VEGF and other related proteins to stimulate new blood vessel growth, tumors support and feed themselves, allowing them to grow. The concept behind angiogenesis inhibition, then, is to thwart this process and thereby fight tumor progression. Bevacizumab is one example of this category of drig.

III) Proteasome inhibitors

The proteasome is a structure inside the cell which breaks down proteins that have been labeled to undergo degradation and recycling. By binding part of the proteasome, a drug can inhibit the breakdown of some of these proteins that have been marked for destruction. Example would be a drug like Bortezomib.

IV) Immunotherapy

Targeted immunotherapy agents bind to their targets, not to interfere with growth signals, but rather to trigger immune signals.Targeted immunotherapy drugs are essentially a collection of monoclonal antibodies, all of which have different targets. Antibodies are proteins that seek out and bind to specific antigens; every antibody has a particular antigen with which it “fits”. Antibodies are named for the antigen that they bind, eg: the anti-CD20 antibody binds to the antigen CD20. When there is a radioactive substance (radioisotope) attached, these drugs are called radio-immunotherapy agents. Example – Rituximab, Tositumomab, Ibritumomab.

V)Antisense oligonucleotide drugs

Antisense oligonucleotide drugs offers the ability to target almost any cellular process with complete specificity. If a protein is helping a cancer cell to grow, then the appropriate antisense oligonucleotide could be used to prevent that protein from ever being made.

VI) Drugs that affect Molecular receptors

Our cells constantly monitor their surroundings for the presence (or sometimes an absence) of regulatory molecules in the environment. These signals control decisions regarding cell division, movement and even death. Many diseases like Cancer, can be traced back to dysfunctional signaling pathways. In cancer these malfunctions may lead to unregulated cell division and the development of tumors. Particular signaling pathways are often affected in a given type of cancer.

Drugs designed to inhibit these specific signaling pathways promise to inhibit cancer growth without harming normal cells. Example – Bexarotene, Denileukin diftitox.

Advantages of Targeted Therapy

Reducing Toxicity:

• One significant advantage that targeted therapies have over most traditional therapies is that they tend to be less toxic to non-cancerous cells.
• Because they tend to have fewer effects on noncancer cells and therefore tend to be less toxic, targeted agents are particularly amenable to use in combination with other agents since their combined side effect profiles would still be acceptable
• The advantage of the less toxic targeted therapy is that it can be given to patients with poor performance status who may not otherwise be candidates for cytotoxic treatment.

The Future of Targeted Therapies

Early trial data presented at basic and clinical science meetings continue to shed light on the more promising drugs, and help to identify the most effective regimens and/or sequence of regimens of these agents when used in conjunction with traditional cytotoxic therapies.