Targeted Therapy For Cancer Treatment

It is necessary to take a short look at the physiology and formation of cancer, before reviewing the targeted cancer therapy.

What is cancer?

There are billions of cells in our body, performing various functions. These cells posess spesific genes for synthesis of particular proteins responsible for their spesific functions. These proteins are synthesized when they are needed. All the cells of the body have limited life periods and when they are unable to perform their functions, they are destroyed naturally by a process called apoptosis (natural cell death), followed by new cell formation. The new cells are produced by cell division and genetically production of new functional proteins for their special functions. During these genetic replication processes, various factors (enviromental or genetic factors, viruses, bacterias etc) may influence genetic translation process with altered genetic codes resulting with ectopic cell growth (an abnormal gene expression in a cell type, tissue where the gene is not corectly expressed). These cells with altered genetic codes, grow in an uncontrolled manner, because they don’t have any signal mechanisms to stop their growth. This growth results with a structure called the tumor. Tumors may be malign(cancerous) or benign (noncancerous). In both cases, this structure is a living cell and maintains its growth by using the oxygen and nutritients which they derive from the blood. They obtain this, by increasing the enviromental blood vessel supply. These cells may be localised in the tissue of origin (in situ) and even if they are surgically removed, they may start growing again with the residue of an abnormal genetic coded cell or may spread to the other organs via blood circulation ( for example; leukemia or blood cancer types). Even if the tumors are benign, they may block the normal functions of the tissue in which they are localised, because of their uncontrolled growth properties.

How does the progress of cancer occur ?

Cancer cells, reject the signals of the natural biological death signals of the normal cells and continue their existence. As they are different in their structure compared to the normal body cells, they escape from the immune response of the body and continue spreading, carrying their genetic codes to other organelles (metastase).

Is the body capable of defeating cancer?

In normal condutions, the body is equipped with systems to correct the altered genetic code, to a certain extent. However, the cancer cell has a high capacity to grow in a fast manner and with aging, the body’s capacity is reduced and cannot cope up with the growing cancer. One of these natural defense mechanisms is proto-oncogenes, which are responsible of maintaining the normal genetic codes of the cell. Tumor repressing genes, prevent the growth abnormal genetic coded cells. The DNA repair genes are responsible for replacing the altered codes with normal ones. Sometimes, these genes theirselves, lose their normal genetic codes and become incapable of performing their functions.

How is cancer treated and are there new promising hopes for treatment?

Cancer was and still is being treated with chemotherapy (killing the cancer cells chemically by entering the cell) and radiotherapy (destroying and shrinking the cancer cell by high doses of radiation). Surgical removing of the localised tumor is also another common treatment if the tumor is in situ(localised at the site of origin). Chemotherapy and radiotherapy is a disadvantage, because this treatment also destroys the normally functioning natural cells of the body as they are not spesific for the cancer cells.

In present, although chemotherapy and radiotherapy methods are still valid , another therapy is being used to destroy the cancer cell by targeting the cells with altered mutations. This is called the targeted cancer therapy.

How is the targeted cell therapy applied in cancer treatment?

The treatment is based on a spesific drug (small molecules that enter the cell easily), which is targeted to stop the genetically altered coded cell mutations. This brings the need to find out whether the drug targets the cancer cell. This is called the biological marker testing. It is to find out if the drug is suitable and spesific for the altered genetic code of that spesific cancer cell, in order to perform the mechanism designated for the therapy. These molecular profiling test are NGS (Next Generation Sequencing) and IHC (Immunohistochemical testing) which are decided by genetic pathologists examination and the patient’s doctor together. NGS gave positive results in 10-50% of patients, depending on the type of cancer. IHC has also given promising results with its mechanism of presenting the cancer cell to the body’s own immune system.

The generally approved mechanisms of the drugs are ;

  • Drugs blocking the surface proteins which lead to uncontrolled cell growth signals,
  • Drugs preventing the replication of altered genetic codes by entering the cell.

What are the tests performed for target cancer therapy?

The tests are based on determining the mutations of the target cancer proteins and observing the cell types targeting the therapy.

The tests are done for the cancer patients who are resistant to chemotherapy and/or radiotherapy. The material is the biopsy sample, obtained from the cancer tissue.

Although the test is done once, if there is no recovery after the drug treatment, it may be repeated to see if there are new possible unexpected mutations.

The drug treatment expenses are still yet to be determined and ways for reduced prices are searched as these therapies are patient and case spesific.

Are targeted cancer therapy drugs approved by FDA(Food and Drug Administration)?

FDA approved targeted cancer therapy drugs are listed and revised on Dec 6,2022, according to the criterias of more than one drug for a certain type of cancer or one drug for various types of cancer includin 31 different cancer types.

Reviewed by Asssoc.Prof. Selvin Aydın

References:

1-https://www.cancer.gov/about-cancer/treatment/types/targeted-therapies/approved-drug-list

2-https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3582044/

3-https://www.testing.com/tests/genetic-tests-targeted-cancer-therapy/