This article will explore the science behind HER2-positive gastric cancer and how patients are currently being treated for the condition using HER2-targeted therapies.
While gastric cancer is a disease of great complexity and different biological profiles in individual patients, an important criterion for the choice of therapy is the expression of human epidermal growth factor receptor 2, HER2, in the tumor cells of the stomach. This article provides educational information about the scientific principles underlying HER2-positive stomach cancer treatment.
What Is HER2?
HER2 is a protein that lies on the surface of cancer cells. It is a receptor for a certain type of signal. Receptors are proteins in the cell membrane that receive chemical signals from outside the cell. These signals are then translated into a variety of different responses such as increased cell growth and division. Some forms of cancer have an increased amount of HER2 protein on the surface of their cancer cells or even more HER2 genes.
HER2 in cancer: If a gastric cancer contains an abnormal amount of HER2 protein or there is an excessive number of copies of the HER2 gene, the cancer can be described as HER2-positive.
Cancer of the stomach with elevated levels of HER2 protein or an increase in the number of copies of the HER2 gene is not cancer of the stomach in which all cases the level of HER2 is elevated.
How HER2 Can Influence Cancer Growth
Cancer cells grow and divide because they receive normal growth signals. These cells become malignant when they use these normal signals in an abnormal fashion. Many of the aberrant signals in cancer are initiated by an overexpression of HER2 proteins on the surface of the cancer cells.
These signals are normally used for the controlled growth of normal cells, but when cancer cells divide excessively, cancerous cells use the same signals for their excessive growth and survival. Thus, HER2 has become an important target for many researchers to develop cancer therapies to stop the excessive growth of tumor cells.
HER2-targeted therapies have been developed to interfere with the Her2 pathway in cancer cells. Such agents can either bind to the extracellular domain of the Her2 receptor or interfere with intracellular signaling pathways downstream of the receptor. These therapies are designed to target pathways associated with cancer cell growth.
How HER2 Testing Works
Before discussing HER2-targeted treatment, must first establish whether a patient’s tumor is HER2-positive. Such tests are usually performed on tissues obtained by a biopsy (e.g., endoscopic ultrasound-guided fine-needle aspiration biopsy) or as part of the pathologic evaluation of tissue removed by surgery.
The expression of the HER2 protein in gastric cancer cells and the degree of amplification of the HER2 gene is measured using various methods and evaluated using established clinical criteria to determine the appropriate treatment for a given patient.
The gastric cancer HER2 status is considered in conjunction with other factors including the cancer location, tumor stage, patient overall health, prior treatment and other tumor markers. Many patients ask their doctors about the different HER2 tests and how the results from these tests can determine what sort of treatment the patient will receive for their cancer.
How HER2-Targeted Treatment Works
HER2-targeted treatments are drugs that interfere with the HER2 pathway. Some are mAb that bind to the HER2 protein on cancer cells to prevent signaling; others interfere with signaling downstream of the receptor. Immunotherapies that target tumors also affect the HER2 pathway, and many are being studied for their potential to treat HER2-positive gastric cancers.
Some targeted cancer drugs for HER2 positive cancer work by attaching to the HER2 protein on cancer cells to stop the cancer cells from signaling to grow. Others can help the immune system find and destroy cancer cells. Every HER2-directed agent works in different ways to interfere with the HER2 pathway. Much remains to be learned on the optimal use of these classes of agents.
Combining Targeted Therapy with Other Treatments
Of course, HER2-targeted therapies are not used in isolation, and so in addition to the therapy described above, other methods of treating a patient’s cancer may be prescribed by the oncologist. These include chemotherapy; immunotherapy; local therapies such as surgery or radiation therapy; other specific targeted therapies; or a combination of all the above.
The way chemotherapy works is different from the way HER2-targeted therapy works. These therapies work through different biological mechanisms and may be used in combination in certain treatment settings.
Combination of different treatment methods increases the risk of side effects but may offer different clinical considerations that should be evaluated by the healthcare team The consideration of potential benefits and risks is very important for the patient’s physician.
The Role of Immunotherapy
In other words, there are several approaches that are currently under research to treat gastric cancer using immunotherapy. This type of cancer treatment is different from other types of targeted therapy and can stimulate the body’s immune system to fight cancer. Many factors must be considered to decide whether a patient with a gastric cancer may be considered for a particular immunotherapy approach None of these is the HER2 status of the tumor.
A lot of interest also exists to investigate the potential of combination of targeted agents with immunotherapies in gastric cancer, taking advantage of different mechanisms of action to affect cancer cells and the immune environment.
Why Some Patients Respond Differently
Different HER2 positive tumors can behave differently to treatment and even within one tumor there can be more than one important biological feature, and the tumor can change over time. The tumor can continue to grow as the cancer cells can develop in the tumor new biological characteristics which enable them to continue to grow in presence of targeted therapy.
Regular monitoring of the patient is necessary during the cancer treatment to check if the cancer is responding to the treatment or not. Other aspects of cancer treatment and even resistance to treatment of cancer are currently under investigation by researchers.
Monitoring Treatment Response
Doctors use a variety of different methods to measure the effects that cancer treatment is having. These may include a variety of different types of imaging, clinical examination, laboratory tests and assessment of symptoms.
Monitoring and follow-up: Tumour size: The use of imaging (e.g. CT scans) to measure changes in size of tumours over time.
Reporting new symptoms or symptoms getting worse. Some symptoms may be due to cancer progression and/or treatment side effects which require a medical assessment.
Understanding Side Effects
Just like with other anticancer therapies there are side effects linked to the treatments for HER2 positive gastric cancer. How severe the side effects are depending on the medication used as well as on the treatment.
These include for example fatigue, gastrointestinal symptoms, reduced blood counts and a range of other effects, usually requiring cessation of the medication for a while. Some of the HER2-targeted treatments also require special monitoring of certain organs or systems. Patients should be made aware of potential side effects prior to commencing treatment. When patients experience symptoms that are of concern, these should be reported to the patient’s oncology team without delay.
The Future of HER2-Positive Gastric Cancer Care
There are a lot of ongoing research activities focusing on HER2-positive stomach cancer, looking into new HER2-targeting agents, new treatment combinations, new biomarkers, and ways to tackle resistance.
Researchers are striving to find new ways to treat patients with her2 positive stomach cancer, including new targeted therapies for HER2 positive gastric cancer as well as a better understanding of the combination of therapies and the monitoring of patients on treatment. For patients researching her2 positive stomach cancer treatment, understanding these developments can provide useful context when discussing treatment options with qualified medical oncologists.
Ultimately, the selection of individual cancer treatment is based on the specific type of cancer a patient has been diagnosed with as well as other unique factors pertaining to that patient’s cancer, past health, current health status and more. It is always in a cancer patient’s best interest to seek the advice of experienced and qualified medical oncologists who can best inform their treatment choices.
Disclaimer: The information provided in this article is intended for educational purposes only and should not be interpreted as medical advice, a clinical guideline, or a recommendation for any specific treatment.