Journal of Tumor Research
Open Access

Identifying Gastrointestinal Stromal Tumors (GIST): Basic Awareness and Potential Therapies

Frojd Carril^{* *}Correspondence: Frojd Carril, Department of Oncology, Karolinska University Hospital, Stockholm, Sweden, Email:

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Description

A Gastrointestinal Stromal Tumor (GIST) is a rare form of cancer that originates in the digestive system, specifically in the cells that form the walls of the Gastrointestinal (GI) tract. GISTs most commonly develop in the small intestine or stomach but can occur anywhere along the digestive system, from the esophagus to the rectum. This type of tumor arises from a special type of nerve cell known as Interstitial Cells of Cajal (ICC), which are involved in controlling the movement of muscles in the digestive tract. GISTs are considered a form of soft tissue sarcoma and although many GISTs are benign (non-cancerous), others can be malignant (cancerous), potentially spreading to other parts of the body.

Causes of Gastrointestinal Stromal Tumors (GIST)

The exact cause of GISTs remains largely unknown, but study indicates that most of these tumors arise from mutations in the KIT or Platelet-Derived Growth Factor Receptor Alpha (PDGFRA) genes. These mutations lead to the uncontrolled growth of cells in the walls of the digestive system. KIT mutations are present in more than 85% of GISTs and these mutations cause the cells to grow uncontrollably, leading to tumor formation.

While GISTs can occur in anyone, certain genetic conditions increase the risk of developing them. The most notable of these is Neurofibromatosis type 1 (NF1), a rare inherited disorder that affects the nervous system and predisposes individuals to developing GISTs. Carney-Stratakis syndrome, another inherited condition, also increases the risk of developing these tumors. However, these genetic syndromes are rare and most cases of GIST are sporadic, with no clear family history or inherited cause.

Symptoms of gastrointestinal stromal tumor

GISTs can range from small, asymptomatic tumors to large growths that cause significant health problems. The symptoms largely depend on the size and location of the tumor within the digestive tract. Some common symptoms include.

Abdominal pain: This is one of the most frequent symptoms of GISTs, especially when the tumor grows large or presses against surrounding tissues.

Abdominal mass or swelling: A palpable lump may be felt in the abdomen if the tumor is large enough.

Loss of appetite and feeling full quickly: This can occur, particularly in tumors located in the stomach or small intestine, as the tumor can affect the digestive process.

Weight loss: Unexplained weight loss often accompanies GISTs, particularly malignant ones.

Bleeding: GISTs, especially when they are large, can sometimes cause internal bleeding, which may result in blood in the stool or vomit.

Difficulty swallowing: If the tumor is located in the esophagus or near it, patients may experience dysphagia (difficulty swallowing).

Interestingly, some individuals with GISTs may not experience any symptoms until the tumor has grown to a large size. In fact, many people with small, benign GISTs may live without significant health problems, only discovering the tumor during imaging tests for other conditions.

Diagnosis of gastrointestinal stromal tumor

Diagnosing a GIST typically begins with imaging tests, such as CT scans, MRI or ultrasound, to identify the size and location of the tumor. During a biopsy, a small sample of the tumor is removed and analyzed under a microscope to determine whether it is benign or malignant and to check for genetic mutations like KIT or PDGFRA.

Additionally, genetic testing can help identify mutations in these genes, which is particularly important for determining the best course of treatment, as GISTs with KIT or PDGFRA mutations respond well to certain targeted therapies.

Treatment of gastrointestinal stromal tumor

Treatment options for GIST depend on several factors, including the tumors size, location, whether it has spread and whether it carries specific genetic mutations. While surgery remains the primary treatment for localized GISTs, other treatment modalities are also used to manage the disease.

Surgical treatment: Surgery is the most effective way to treat GISTs when the tumor is localized (not spread to other organs). For tumors that are 3 cm or larger, surgical resection (removal of the tumor) is typically performed. In some cases, laparoscopic surgery (a minimally invasive surgery) may be used for smaller tumors that are 5 cm or less. The goal of surgery is to remove the tumor along with a margin of healthy tissue to minimize the risk of recurrence. Surgery is considered the standard treatment for localized GISTs and is usually recommended if the tumor can be safely removed. However, surgery is not a curative option for GISTs that have spread to distant organs, such as the liver or lungs.

Targeted therapy: For GISTs that are unresectable (cannot be removed surgically) or have metastasized, targeted therapies are often used. These therapies specifically target the genetic mutations in GIST cells that drive their uncontrolled growth. The most common targeted therapy for GIST is Imatinib (Gleevec), which works by inhibiting the KIT protein produced by KIT mutations. Imatinib is particularly effective for GISTs with KIT mutations and can shrink tumors, slow their growth or prevent recurrence after surgery. Other tyrosine kinase inhibitors, such as Nilotinib (Tasigna), Pazopanib (Votrient) and Dasatinib (Sprycel), may also be used depending on the specific characteristics of the tumor.

Chemotherapy and radiation: Chemotherapy and radiation are not typically effective for treating GISTs. However, they may be used in certain cases when the tumor is resistant to targeted therapy or if it has spread widely. Chemotherapy is generally less effective because GIST cells do not respond well to conventional chemotherapy drugs.

Conclusion

Gastrointestinal Stromal Tumors (GISTs) are a rare but serious form of cancer that originate in the digestive system. Though the exact cause remains unclear, genetic mutations in the KIT or Platelet-Derived Growth Factor Receptor Alpha (PDGFRA) genes play a significant role in tumor development. Treatment for GISTs varies depending on the tumors size, location and genetic characteristics, with surgery being the most common option for localized tumors and targeted therapies like imatinib offering hope for patients with metastatic disease. While surgery can be curative for some patients, the use of advanced therapies has dramatically improved outcomes, especially for those with advanced or inoperable GISTs.