Cancer is a complex and multifactorial disease that results from the accumulation of genetic and epigenetic alterations in cells.

Researchers are constantly striving to understand the underlying mechanisms of cancer pathogenesis to develop better diagnostic tools, prevention strategies, and treatment protocols for the patients. In this article, we will discuss the mutated gene that increases the likelihood of salivary gland cancer, its clinical significance, and potential therapeutic targets.

Salivary Gland Cancer: An Overview

Salivary gland cancer is a relatively rare type of cancer that affects the glands responsible for producing saliva.

The salivary glands are located in the mouth and throat regions and play a vital role in producing saliva that helps in digestion, lubrication of mouth and throat, and protection against infections. There are three main types of salivary glands: parotid, submandibular, and sublingual. Salivary gland cancer can arise from any of these glands, and the symptoms may vary depending on the location, size, and type of cancer.

The symptoms of salivary gland cancer may include:.

A lump or swelling in the mouth or neck
Persistent pain in the mouth, ear, or neck region
Difficulty in swallowing or opening the mouth
Numbness or weakness of the face
Changes in the facial muscle movements
Fluid drainage from the ear

Salivary gland cancer is diagnosed through a series of tests, including physical examination, imaging studies, and biopsy. The treatment options may include surgery, radiation therapy, chemotherapy, and targeted therapy.

The prognosis of salivary gland cancer depends on the type, stage, and grade of cancer, as well as the patient’s overall health status.

The Mutated Gene: PIK3CA

The phosphatidylinositol 3-kinase (PI3K) signaling pathway is one of the most frequently altered pathways in human cancers.

The PI3K pathway plays a crucial role in cell proliferation, survival, and metabolism, and dysregulation of this pathway can lead to the development and progression of various cancers, including salivary gland cancer.

The PIK3CA gene encodes the catalytic subunit of the PI3K enzyme, and mutations in this gene have been reported in many human cancers, including breast, colon, ovarian, and head and neck cancers.

The PIK3CA gene mutations occur mainly in the helical (exon 9) and kinase (exon 20) domains of the protein and result in the constitutive activation of the PI3K pathway.

Several studies have reported the presence of PIK3CA gene mutations in salivary gland tumors. A study published in the journal Diagnostic Pathology in 2014 analyzed the PIK3CA gene mutations in 63 cases of salivary gland tumors.

The study found that 32% of the cases had PIK3CA mutations, and the mutations were more frequent in the acinic cell carcinoma subtype of salivary gland cancer.

Another study published in the journal Oral Oncology in 2019 analyzed the PIK3CA gene mutations in 292 cases of salivary gland tumors.

The study found that 54% of the cases had PIK3CA mutations, and the mutations were more frequent in the mucoepidermoid carcinoma subtype of salivary gland cancer.

The clinical significance of PIK3CA gene mutations in salivary gland cancer is still under investigation.

However, some studies have suggested that PIK3CA mutations may be associated with a poor prognosis, increased risk of recurrence, and resistance to conventional treatments.

Potential Therapeutic Targets

The identification of PIK3CA gene mutations in salivary gland cancer has provided insights into the potential therapeutic targets for this disease.

The PI3K pathway is a complex and dynamic signaling pathway that involves multiple components and feedback loops. Therefore, targeting this pathway may require a combination of drugs that target different components of the pathway.

The PI3K inhibitors are a class of drugs that target the PI3K enzyme and have shown promising results in preclinical studies and clinical trials for various cancers.

However, the clinical benefit of PI3K inhibitors in salivary gland cancer is not well established, and more studies are needed to evaluate their efficacy and safety.

The mTOR inhibitors are another class of drugs that target the downstream effectors of the PI3K pathway, such as the mammalian target of rapamycin (mTOR).

The mTOR inhibitors have been approved for the treatment of various cancers, including renal cell carcinoma and breast cancer. Some studies have suggested that mTOR inhibitors may have a therapeutic benefit in salivary gland cancer, especially in the PIK3CA mutant tumors.

The EGFR inhibitors are a class of drugs that target the epidermal growth factor receptor (EGFR), which is a key component of the PI3K pathway and is often overexpressed or mutated in human cancers.

The EGFR inhibitors have been approved for the treatment of several cancers, including non-small cell lung cancer and head and neck cancer. Some studies have suggested that EGFR inhibitors may have a therapeutic benefit in salivary gland cancer, especially in the PIK3CA mutant tumors.

Conclusion

Salivary gland cancer is a rare and complex type of cancer that requires a multidisciplinary approach for diagnosis and treatment.

The identification of PIK3CA gene mutations in salivary gland cancer has provided insights into the underlying molecular mechanisms of this disease and potential therapeutic targets. The PI3K pathway inhibitors, mTOR inhibitors, and EGFR inhibitors are some of the drugs that are being evaluated for the treatment of salivary gland cancer, especially in the PIK3CA mutant tumors.

However, more studies are needed to evaluate the efficacy and safety of these drugs in salivary gland cancer and to develop better diagnostic tools and prevention strategies for this disease.