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Why is tumor profiling the new frontier of oncology?

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oncology

Cancer care is seeing a move away from the histopathologically-defined disease (being treated primarily with cytotoxic chemotherapy), toward the use of molecularly-targeted drugs.


In fact it was established that mutations in the genome of a normal cell can affect the function of its many genes and pathways. These alterations could eventually transform the cell from a normal to a malignant state by allowing an uncontrolled proliferation of the cell and formation of a cancer tumor.

Each tumor in an individual patient can have hundreds of mutated genes and perturbed pathways. Cancers histopathologically defined as the same type or subtype could potentially be very different at the molecular level and thus behave differently in response to therapy.

The challenge is to distinguish the key mutations driving the cancer from the background of mutational noise and find ways to effectively target them.

A such a molecular approach to classifying cancer will lead to better diagnostic, prognostic and personalized treatment strategies. This article provides an overview of advances in the molecular characterization of cancers and their applications in therapy.

What are the targeted cancer therapies?

Targeted cancer therapies are drugs or other substances that block the growth and spread of cancer by interfering with specific molecules (“molecular targets”) that are involved in the growth, progression, and spread of cancer: these can not therefore be separated from a series of in-depth studies and techniques of genetic profiling Targeted cancer therapies are sometimes called “molecularly targeted drugs,” “molecularly targeted therapies,” “precision medicines,” or similar names.

A primary goal of targeted therapies is to fight cancer cells with more precision and potentially fewer side effects.

Once a candidate target has been identified, the next step is to find a therapy that affects the target in a way that interferes with its ability to promote cancer cell growth or survival. For example, a targeted therapy could reduce the activity of the target or prevent it from binding to a receptor that it normally activates, among other possible mechanisms.

Most targeted therapies are either small molecules or monoclonal antibodies. Small-molecule compounds are typically developed for targets that are located inside the cell because such agents are able to enter cells relatively easily. Monoclonal antibodies are relatively large and generally cannot enter cells, so they are used only for targets that are outside cells or on the cell surface.

How targeted therapies differ from chemotherapies?

Targeted therapies differ from standard chemotherapy in several ways:

  • Designed to interfere with specific molecules necessary for tumor growth and progression. Traditional cytotoxic chemotherapies usually kill rapidly dividing cells in the body by interfering with cell division. A primary goal of targeted therapies is to fight cancer cells with more precision and potentially fewer side effects.
  • Deliberately chosen or designed to interact with their target, whereas many standard chemotherapies were identified because they kill cells.
  • Aare often cytostatic (that is, they block tumor cell proliferation), whereas standard chemotherapy agents are cytotoxic (that is, they kill tumor cells).
  • Currently the focus of much anticancer drug development. They are a cornerstone of precision medicine, a form of medicine that uses information about a person’s genes and proteins to prevent, diagnose, and treat disease.

Many targeted cancer therapies have been approved by the international regulators (FDA, EMA, ESMO, NCCN) to treat specific types of cancer, these include: hormone therapies, signal transduction inhibitors, gene expression modulators, apoptosis inducers, angiogenesis inhibitors, immunotherapies, and toxindelivery molecules.

How can patients be sure a genetic test is valid and useful?

Before undergoing genetic testing, it is important to be sure that the test is valid and useful. A genetic test is valid if it provides an accurate result. Two main measures of accuracy apply to genetic tests: analytical validity and clinical validity. Another measure of the quality of a genetic test is its usefulness, or clinical utility.

  • Analytical validity refers to how well the test predicts the presence or absence of a particular gene or genetic change. In other words, can the test accurately detect whether a specific genetic variant is present or absent?
  • Clinical validity refers to how well the genetic variant being analyzed is related to the presence, absence, or risk of a specific disease.
  • Clinical utility refers to whether the test can provide information about diagnosis, treatment, management, or prevention of a disease that will be helpful to a consumer.
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