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Our body is composed of billions of cells. Normally the growth and reproduction of every cell is regulated by a complex series of signaling pathways. This regulation determines how the tissues and organs in the body function, as well as determining their size. Each individual cancer is a clone that arises from a single cell. During a person's lifetime changes may occur in the genetic material of the cells. Most of the reasons for these changes are still unknown. These changes interrupt the cell regulation process resulting in uncontrolled cell proliferation. The result is a mass or growth, also called a tumor.
The cells within malignant tumors have the ability to invade neighboring tissues and organs, thus causing the disease to spread. It is also possible for cancerous cells to break free from the tumor site and enter the bloodstream, causing the disease to spread to other organs. This process of the spreading of cancer cells is called metastasis.

A biopsy is a sampling of a small group of cells or tissue taken by the physician from the suspicious tumor. It is generally examined under a microscope by a pathologist.
A biopsy may be performed in several different ways and the decision as to which one is the most effective depends on the tumor type, its location and the general health of the patient.
A biopsy is an important step in distinguishing malignant from benign tumors and it might also provide the physician with other information for a diagnosis. 
 

The pathology report after surgery contains a description of the gross and the microscopic examination of the surgical specimen. First, a macroscopic or gross description, as it looks to the naked eye, is provided. This includes the tumor location, size, weight, color and any other distinguishing characteristics.
Tissue specimens are then embedded in paraffin blocks, cut into slices and processed. Once prepared, they become the basis for pathology slides so that they can be carefully examined under a microscope.
The microscope examination gives details of how the tumor cells look compared with normal cells (e.g. the size and shape of the cells, the nucleus, frequency of dividing cells that are seen, etc.). The whole procedure (preparation and examination) might take two weeks or even more.
The pathology report plays an important role in cancer diagnosis and staging. Since it describes the extent of the tumor and its unique characteristics, it can help a great deal in determining treatment options.

The ultimate goal of cancer treatment is to stop the primary tumor cells from growing and spreading, thereby destroying as many of these cells as possible.
There are different types of cancer treatment. The most common cancer treatment options are surgery (the first treatment option if the tumor can be taken out of the body), radiation therapy and anti-cancer drugs (e.g. chemotherapy, hormonal therapy).
Cancer treatment may consist of a single therapy or a combination of therapies. Treatment decisions are based upon the cancer type and stage, the tumor characteristics, and the patient's general health and preferences.

Anti-cancer drugs have different mechanisms of action. However, most of these mechanisms are based on inhibiting certain important steps in cell growth and division, thus tending to work best in rapidly dividing cells. Since cancer cells are dividing rapidly, they are the most susceptible to damage from this therapy. There are also drugs that help the body's immune system to destroy cancer cells more effectively.
Similarly, radiotherapy interferes in the cell division process by damaging the genetic material of these cells, preventing them from reproducing and causing them to die.

Local therapy is directed towards the tumor site (e.g. surgery which is performed to remove the tumor and/or radiation therapy).
Local therapy aims to remove and/or destroy cancer cells in the particular tumor site and surrounding area.
Systemic therapy travels through the bloodstream reaching cancer cells all over the body (e.g. chemotherapy which is commonly administered through a vein or given orally).
Systemic therapy is designed to inhibit the growth, division and spread of cancer cells throughout the body (e.g. different anti-cancer drugs).

Most side effects of chemotherapy and radiotherapy are caused by the effect of cell destruction of these treatments. Both chemotherapy and radiotherapy target cells which divide and multiply rapidly, thereby they are most effective in killing cancer cells (whose mechanism of division and multiplying is uncontrolled). Some cell types (e.g. skin cells, bone marrow cells), even in a normal state, divide and multiply more rapidly than others (e.g. muscle cells, nerve cells). For this reason, these cells are much more affected by the chemotherapy and/or radiotherapy, which lead to the treatment side effects. However, normal cells have the ability to renew themselves much better than cancer cells, by special mechanisms. As a result, they usually recover quite well between the treatment cycles and after treatment, as opposed to the cancer cells which lack these mechanisms of repair and therefore are subsequently destroyed.
Side effects may vary between different types of anti-cancer drugs given, and even after the same drug different people might react differently.

Imaging tests following cancer diagnosed by a biopsy provide information regarding the disease stage (the tumor size and location, whether or not it has already spread in the body and where to) and help in determining what kind of treatment will be most effective (local treatment, systemic treatment, both kinds and priority).
During the follow-up period, imaging tests help in looking for possible signs of cancer recurrence (local and/or systemic) after treatment. According to the information obtained, treatment decisions will be made; whether to continue with the regular follow-up and periodic tests only (in case of no evidence of disease) or, in case of local/ systemic recurrence, to restart treatment that might be most effective for the new situation.
Imaging tests performed over the course of treatment help to determine if the specific type of treatment given has been effective. The extent of the disease is compared to previous images taken before the treatment was started. The results will tell if any changes in treatment are necessary.
It is important to emphasize that there is no specific imaging test which is known to be most effective in all cancer types and for all cancer patients. Different types of cancers as well as different stages of the same disease might require different types of imaging in order to achieve the highest accuracy.

Tumor markers are substances that are produced by tumor cells (or by the body in response to tumor cells) and secreted also to the blood where they can be measured with a simple blood test. There are different tumor markers. Most of them are not associated with a specific type of cancer but with two or more cancer types. Some tumor markers are always elevated in specific cancers, but not everyone with a specific type of cancer will have a higher level of a tumor marker associated with that cancer. No tumor marker is specific for cancer. In other words, there is no "universal" tumor marker that can detect any type of cancer and most are also found in low levels in healthy people, or can also be associated with non-cancerous diseases, thus being less predictable.
For these reasons tests for tumor markers are usually combined with other parameters. They are used for help in detecting, diagnosing and managing some types of cancer as follows:-
In those cases that the pathology results are inconclusive, elevated tumor markers that are associated with a specific type of cancer may help in identifying the exact type of cancer. In other cases the level of the tumor markers at the time of diagnosis may reflect the extent of disease, thus being helpful throughout the process of treatment decision- making.
Tumor marker levels are also measured periodically during cancer therapy in conjunction with other clinical parameters, such as radiological findings and patient complaints, to monitor a treatment success: a decrease in the level of a tumor marker may indicate that the cancer is responding to treatment, whereas an increase may indicate that the cancer is not responding and the specific drug given should be changed. Conclusions based on tumor markers are seldom based on one test result but on a series of test results called serial measurements. A series of increasing or decreasing values is more significant than a single value. It is important to note that timing of the tests is also significant and tests done too soon may be falsely elevated.

Clinical trials in oncology are research studies conducted all over the world, in which a new treatment – a drug, diagnostic procedure or any other therapy – is tested in cancer patients to determine if it is safe and effective. It is also compared to commonly used treatments which have been proved as useful in the past.
Such trials help scientists answer questions about the new cancer therapy, such as which diseases it should be used for, which doses are most effective, and which patients can most benefit from it.
Before testing on humans, laboratory tests and medical procedures on animal subjects (i.e. preclinical trials) are conducted, in order to gather evidence justifying a clinical trial.
These preclinical studies are required to collect data in support of the safety of the new treatment before clinical trials on humans can be started.
It is important to note that drugs are tested extensively during preclinical research and the whole process of development usually takes many years.
Clinical trials involving new drugs are typically conducted in 4 phases. Each phase of the drug approval process is treated as a separate clinical trial, thus having its own purpose in helping scientists answer a different question. Only a drug which successfully passes through all phases might be approved for use.
A phase I trial is the most basic clinical trial. It looks at how safe the drug is and tries to evaluate its optimal dose. The purpose of a phase I trial is to determine the dose and the schedule in which the experimental drug can be given safely, without harm. Since a phase I trial is the first time a new drug is tested on humans, it usually involves only a small number of patients, mostly with different types of cancer and at advanced stages, who are not getting better with standard treatments.
A phase II trial tests the effectiveness of the drug against a specific type of cancer, based on the dose and schedule determined to be safe in the phase I study. Phase II trials are also tested in relatively small groups of patients whose cancer has not responded to standard treatments, or those who do not have standard treatments available to them.
A phase III clinical trial is conducted in patients for whom the drug was shown to be efficient in phase II clinical trials. This phase is the final stage a new treatment goes through before considering its approval for general use. It compares the safety and effectiveness of the new treatment to the best current standard of cancer treatment, trying to find out whether the treatment being tested is better, as good as, or worse than the standard treatment, by monitoring adverse effects and collecting information that will allow the intervention to be used safely. Phase III clinical trials usually involve a large number of patients at several different locations, and like in phase I and phase II trials, they are all watched closely. Participants are usually randomly assigned (i.e. having the same probability) to receive the standard treatment or the new one, and the trial itself, if possible, is double-blinded. This means that neither the physician nor the participant know who is getting which treatment. This helps in making sure that the study results are accurate and without bias or outside influence.
A phase IV clinical trial, often called "a post-marketing surveillance trial", is conducted after the drug has been approved for supply to consumers. It aims to gather more information about the possible risks and benefits of the drug that could be associated with long-term effects as well as its impact on the patient's quality of life. A phase IV study can result in a drug being taken off the market, or restrictions for use could be placed on the product, depending on the study's findings.
Almost all clinical trials have their own specific protocol, in which the detailed plan that follows strict scientific and ethical guidelines is documented. The study protocol also includes guidelines as to who can or cannot participate in the trial. A patient who fits the criteria for participation (e.g. type of cancer, stage of disease, treatments previously given, etc.) may be eligible to take part in the trial after being informed by his health care provider about the course of the trial, its goals, and the potential benefits and risks of participating. The participant will have to sign an informed consent form which validates the patient's willingness to participate in the trial.
The decision to participate or not participate in a clinical trial is that of the patient only, after being given all the relevant information by his physician. A patient may refuse to participate or may withdraw and discontinue participation in a clinical trial at any time for any reason, and this decision will not affect the provision of health care to him or its quality.

Changes in the genetic material of the body's cells during a person's lifetime might induce a carcinogenic process (see above: "Cancer characteristics"). These changes, known as genetic mutations, initially occur in one cell, in most cases for unknown reasons, and then pass on to any new cells that are offspring of that cell.
However, in some cases the cancer is caused by a genetic mutation that is passed on through generations. Such an inherited mutation is present in the egg (from the mother) or sperm (from the father) which after fertilization creates one cell called a zygote that than divides to create a fetus. Since all the cells in the body are developed from that zygote, the inherited mutation is in every cell in the body. Of all cancers, 5%-10% are thought to be hereditary, caused by inherited mutations passed from parent to child.
Common examples of cancer types caused by inherited mutations are hereditary breast, ovarian and colon cancer. People who have such a mutation (mutation carriers) are at an increased risk of developing the specific cancer or cancers associated with that mutation, compared to people who are not carriers.
What is genetic testing?
Genetic testing is a medical test (in most cases a simple blood test) performed for the identification of mutation carriers who are at an increased risk of developing a specific type (or types) of cancer.
What is the purpose of genetic testing?
The purpose of genetic testing is to distinguish between those who are carriers, thereby having an increased risk of developing cancer, and those who are not. It enables the carriers to receive the most effective care in order to reduce their risk and/or be able to diagnose their cancer (in the case that it develops) as early as possible. Those who are not carriers, as mentioned above, are not at an increased risk.
Nowadays, in most medical centers, there are Genetics Clinics in which counselors and doctors provide an individualized risk management program for each person at high risk. Such a program includes recommendations for cancer screening and options for preventive measures.
Who should consider genetic testing?
Genetic testing is usually recommended to the patient himself by his physician, when there is a strong suspicion of a hereditary cancer syndrome. Features that might suggest a hereditary cancer syndrome include:
* Cancer that was diagnosed at an unusually young age
* Several different types of cancer that occurred independently in the same person
* Cancer that has developed in both organs in a set of paired organs, such as both kidneys or both breasts
* Several close blood relatives that have the same type of cancer
* Unusual cases of a specific cancer type (for example, breast cancer in a man) 

As mentioned previously (see above: "Cancer characteristics"), during a person's lifetime changes may occur in the genetic material of the cells. Some of these changes interrupt the cell regulation process, causing an uncontrolled cell proliferation. The result is a mass - or growth, also called a tumor.
Each patient has unique variations of his tumor genome, which are considered to be the "fingerprints" characterizing his malignancy. Some of these variations / mutations might influence the tumor behavior and its response to the treatment given; thus, two patients diagnosed with the same type of malignancy (e.g. lung cancer), may respond differently to the same anti-cancer drug, due to the differences between their genomic characteristics.
Personalized medicine is the use of genomic information of each patient in order to "customize" unique health management. Identification of tumor genetic markers that play a role in the tumor cells' behavior and response to a specific treatment given, may allow doctors to "tailor" the most suitable treatment not only for a specific cancer, but for a patient's specific cancer.  
The past decade has seen incredible progress in the development of drugs which interfere with cancer cells' behavior by targeting specific "fingerprints" of cancer. This new approach to cancer treatment – marked and specific, targeted and customized, may offer patients invaluable, additional options and improve both the course of their disease and its prognosis.

 

A biopsy is a sampling of a small group of cells or tissue taken by the physician from a suspicious tumor. A biopsy sample is of major importance in the diagnostic process of cancer disease (see: "The biopsy and its importance").

However, traditional tissue biopsy, which is an invasive procedure, can be risky and painful. Moreover, some patients cannot have tissue biopsy because of the tumor's location, or other health conditions.

Liquid biopsy, which was introduced during the last decade might be an efficient alternative, since it is less invasive, easily repeated, quicker and more useful when the tumor's location makes tumor biopsy unfeasible (offering ease in tumor sampling). It might also devise personalized therapeutic regimens and screening for therapeutic resistance.  

Liquid biopsy is actually a simple blood sampling from which can be isolated tumor-derived entities like circulating tumor cells, DNA and extracellular vesicles - all present in the body fluids of patients with cancer. Taken together, these tumor-derived components can provide crucial longitudinal information and data for more accurate diagnosis regarding both primary and metastasized tumors.

The entire process takes much less time, usually 1 to 2 weeks, in comparison to at least 2 to 4 weeks for standard biopsy. Being easily repeated, it might be able to target many genes in advanced cancer patients, including mutations for which there are targeted drugs.  It can also be used for real-time monitoring, to see if therapy is working - acting as an indicator of treatment response.

However, liquid biopsy still lacks standardization of procedures processed in different laboratories, with comparison of different technology platforms providing difficult. Compared to tissue biopsy, it has a lower sensitivity, and may miss mutations if the tumor does not shed enough DNA into the blood.

In the meantime, liquid biopsy should be considered for patients who are not healthy enough for tissue biopsy, if tissue is unacceptable due to its anatomical location, if the tissue material acquired through biopsy is insufficient, or if the waiting time for the scheduling of the procedure or obtaining the results is too long to impact treatment decisions.

Nevertheless, it is reasonable to suppose that addressing the challenges associated with the use of liquid biopsy through advances in research and technology, may allow its use in routine settings, and open new areas in clinical oncology.

Our body is composed of billions of cells. Normally the growth and reproduction of every cell is regulated by a complex series of signaling pathways.  This regulation determines how tissues and organs in the body function, as well as determining their size (see: "Cancer characteristics").

Each individual cancer is a clone that arises from a single cell. During a person's lifetime changes may occur in the genetic material of the cells. Most of the reasons for these changes are still unknown. These changes interrupt the cell regulation process resulting in uncontrolled cell proliferation. The result is a mass or growth, also called a tumor.

The cells within malignant tumors (i.e. cancer cells) have the ability to invade neighboring tissues and organs, thus causing the disease to spread. It is also possible for cancerous cells to break free from the tumor site and to enter the blood stream, causing the disease to spread to other organs. This process of the spreading of cancer cells is called metastasis.

There are more than 200 types of cancer and, although they all share the same basic characteristics, each broad cancer type (depending on its organ of origin), might also have several subtypes and they look and behaves differently because they are different on a genetic and molecular level. All these might influence the course of disease of each individual patient as well as the decision-making process regarding the most effective treatment in a specific situation.    

The changes occurring in the genome during the transformation of healthy/normal cells into cancer cells (hereinafter: mutations) might cause gene products that stimulate the malignant process, resulting in the spread of cancer cells.

Genome sequencing of cancer cells is a process in which the makeup of the cancer cells removed in the biopsy sample is analyzed, in order to identify mutations, thereby gene products that help cancer cells survive and grow.

The identification of cancer-causing mutations may enable the development and use of drugs designated to directly attack cancer cells by acting on specific genomic alterations or gene products that are involved in the cancer process. It may also be helpful in predicting sensitivity or resistance of the cancer cells to a specific drug, thus altering the choice of treatment and enabling the most effective treatment.

Another advantage of genome sequencing is its potential to discover unknown mutations which are involved in cancer evolution, thereby promoting the development of new targeted therapies.

Mutation analysis is now routinely utilized for the diagnosis of different types of cancer and has become an integral part of cancer therapy, thus allowing personalized selection of cancer drugs based on the presence of targeted mutation. However, it is different from whole genome sequencing since it examines only the genes most likely to be mutated.

Nowadays, whole genome sequencing, which has not been approved by the Israeli drug panel as state-subsidized, is mostly recommended in patients with advanced cancer – who are heavily pre-treated, or in patients with rare tumors, in order to guide treatment decisions in those patients who are difficult to treat.

Gene therapy is a therapeutic strategy using genetic engineering technics to treat or prevent diseases by correcting underlying genetic problems.

The genetic code (i.e. the genetic material) of each cell carries the instructions for making proteins which are crucial for the cells' growth, division and functioning.

Genetic mutations can lead to the production of proteins that do not function properly, or that are missing altogether, causing various diseases including cancer.

Gene therapy, which involves the replacement of a defective gene with a functional, healthy copy of that gene, is a potentially beneficial cancer treatment approach, since it introduces a normal copy of the gene to the cancer cell to recover the function of the protein.

The insertion of a gene into a cancer cell is carried out by different types of carriers (called vectors), that are genetically engineered to directly deliver the gene into the cell (e.g. neutralized viruses).  

Over the last decade, significant advances in technology in the field of oncologic gene therapy research are taking place. The development of new therapies which use healthy genes that may be inserted directly into the cancer cells and replace those which are defective or missing, may be a breakthrough and offer a new horizon for oncology and hematology patients.