Overview of treatment for salivary gland cancer

The treatment of salivary gland cancer depends on several factors, including the type, stage, and location of the cancer, as well as the patient's overall health and preferences. The main treatment options for salivary gland cancer include:

1. Surgery: Surgery is the primary treatment for most types of salivary gland cancer. The goal of surgery is to remove the tumor and surrounding tissue, and in some cases, nearby lymph nodes or other structures. The extent of surgery depends on the location and size of the tumor, as well as the stage of the cancer.

2. Radiation therapy: Radiation therapy may be used alone or in combination with surgery to destroy any remaining cancer cells and reduce the risk of recurrence. It may also be used as the primary treatment for small tumors or for tumors that cannot be completely removed with surgery.

3. Chemotherapy: Chemotherapy is not typically used as the primary treatment for salivary gland cancer. Chemotherapy is sometimes used if there is recurrent or metastatic disease.

4. Targeted therapy: Targeted therapies are drugs that specifically target certain molecules or proteins that are involved in cancer growth and spread. They may be used in combination with other treatments for advanced or recurrent salivary gland cancer.

5. Palliative care: Palliative care is a type of supportive care that focuses on improving the quality of life for patients with advanced or incurable cancer. It may include pain management, symptom relief, and emotional support.

The treatment of salivary gland cancer is often complex and requires a multidisciplinary team of specialists, including head and neck surgeons, radiation oncologists, medical oncologists, and pathologists. The choice of treatment depends on several factors, including the type and stage of cancer, as well as the patient's overall health and preferences. It is important to discuss the potential benefits and risks of each treatment option with a specialist in cancer treatment.

Surgery for salivary gland cancer

Surgery is one of the main treatment options for salivary gland cancer. The type of surgery performed depends on the size, location, and stage of the cancer, as well as the patient's overall health.

The primary goal of surgery is to remove as much of the cancerous tissue as possible while preserving the surrounding healthy tissue and organs. There are several surgical procedures that may be used to treat salivary gland cancer, including:

1. Partial or total removal of the affected salivary gland: The surgeon may remove part or all of the gland, depending on the size and location of the tumor. In some cases, the surgeon may also remove nearby lymph nodes to check for cancer spread.

2. Nerve-sparing surgery: This approach is used when the tumor is located near a nerve that controls facial movement or sensation. The surgeon will try to avoid damaging the nerve while removing the tumor.

3. Reconstruction surgery: After removing the tumor and affected tissue, the surgeon may need to reconstruct the area using a tissue graft or flap. This is done to help restore normal function and appearance.

4. Neck dissection: If cancer has spread to the lymph nodes in the neck, the surgeon may perform a neck dissection to remove them.

5. Radiation therapy: In some cases, radiation therapy may be used after surgery to help kill any remaining cancer cells and reduce the risk of recurrence.

As with any surgery, there are risks and potential complications associated with salivary gland cancer surgery. These may include bleeding, infection, nerve damage, and changes in facial appearance or function. Your surgeon will discuss these risks with you prior to the surgery and provide guidance on how to prepare for and recover from the procedure

Radiation therapy for salivary gland cancer

Radiation therapy is a common treatment option for salivary gland cancer, particularly in cases where surgery is not feasible or when the cancer has spread beyond the salivary gland. Radiation therapy uses high-energy radiation to kill cancer cells by damaging their DNA.

There are several types of radiation therapy that may be used for salivary gland cancer, including:

1. External beam radiation therapy (EBRT): This is the most common type of radiation therapy for salivary gland cancer. It involves using a machine to deliver a beam of radiation to the affected area from outside the body. EBRT may be used alone or in combination with surgery to treat salivary gland cancer.

2. Intensity-modulated radiation therapy (IMRT): This type of radiation therapy uses a computer to control the intensity of the radiation beam, allowing for more precise targeting of the cancerous tissue while minimizing damage to nearby healthy tissue.

3. Proton therapy: Proton therapy is a type of radiation therapy that uses high-energy protons to kill cancer cells. It may be used for certain types of salivary gland cancer that are located close to critical organs or tissues.

4. Brachytherapy: This involves placing small radioactive seeds or pellets directly into the tumor or surrounding tissue. This type of radiation therapy is typically used for smaller tumors or as a boost after EBRT.

5. Carbon ion therapy is a form of radiation therapy that uses high-energy carbon ions to treat cancerous tumors. Carbon ions are charged particles that can penetrate deep into the body and deliver a high dose of radiation to the tumor while minimizing damage to surrounding healthy tissue. Carbon ion therapy is a type of particle therapy, which also includes proton therapy.

Radiation therapy may be used alone or in combination with other treatments, such as surgery or chemotherapy, depending on the stage and location of the cancer. The treatment schedule and duration will depend on the type and stage of the cancer, as well as the patient's overall health and medical history.

Like any medical treatment, radiation therapy can have side effects. Common side effects of radiation therapy for salivary gland cancer may include fatigue, skin irritation or dryness, mouth sores, difficulty swallowing, and changes in taste or smell. Your healthcare team will work with you to manage any side effects and provide guidance on how to care for yourself during and after treatment.

Targeted therapy in salivary gland cancer

NTRK gene fusions are rare in salivary gland cancer, occurring in only a small percentage of cases. However, when they do occur, they have been found most commonly in mammary analogue secretory carcinoma (MASC), a subtype of salivary gland cancer that resembles breast cancer.

Studies have reported NTRK fusions in approximately 50-90% of MASC cases, making it one of the most common types of cancer associated with NTRK gene fusions. NTRK fusions have also been reported in other types of salivary gland cancer, although at much lower frequencies.

The presence of an NTRK gene fusion in salivary gland cancer may have important implications for treatment, as NTRK inhibitors have been shown to have significant activity in patients with NTRK fusion-positive cancers.

NTRK inhibitors are a type of targeted therapy that block the activity of neurotrophic receptor tyrosine kinase (NTRK) proteins. These proteins play an important role in cell growth and survival, and when they are altered or overexpressed, they can drive the growth and spread of certain types of cancer.

NTRK inhibitors are currently approved for the treatment of solid tumors that have NTRK gene fusions. NTRK gene fusions occur when a piece of one of the NTRK genes becomes attached to another gene, resulting in an abnormal fusion protein that drives cancer growth.

NTRK inhibitors are usually considered as a treatment option for patients with advanced or metastatic cancer that has not responded to standard treatments, or for patients who have tumors that have tested positive for NTRK gene fusions. The decision to use an NTRK inhibitor should be made by a qualified medical professional based on the patient's individual cancer type and stage, as well as other factors such as overall health and medical history.

HER2 amplification, which refers to an increase in the number of copies of the HER2/neu gene, is found in a subset of salivary gland cancers, including salivary duct carcinoma (SDC).

HER2 amplification has been reported in around 30% of SDC cases, with some studies reporting rates as high as 40-50%. The presence of HER2 amplification in salivary gland cancer may have important implications for treatment, as HER2-targeted therapies such as trastuzumab (Herceptin) and pertuzumab have shown promise in clinical trials for HER2-positive salivary gland cancers.

However, the decision to use HER2-targeted therapies in salivary gland cancer should be based on the individual patient's cancer type, stage, and other factors, and should only be done under the guidance of a qualified medical professional. It is also important to note that HER2-targeted therapies are not effective in all patients with HER2-amplified salivary gland cancer, and further research is needed to better understand the optimal use of these treatments in this setting.

The androgen receptor (AR) is a protein that is found in the body, specifically in male reproductive tissues like the prostate gland and testes. It is activated by hormones called androgens, such as testosterone, which cause the AR to go to the nucleus of a cell and turn on specific genes. These genes are important for different processes in the body, like growth and development. When the AR signaling is not working correctly, it can lead to different diseases such as cancer.

Studies have shown that AR expression is frequently observed in salivary duct carcinoma (SDC), with rates ranging from 47% to 100%. This high rate of AR expression in SDC suggests that AR signaling may play a role in the development and progression of this cancer.

Furthermore, preclinical studies have suggested that targeting AR signaling may be a potential therapeutic approach for SDC. For example, a study published in the Journal of Clinical Oncology in 2018 reported that a drug called enzalutamide, which inhibits AR signaling, showed promising activity in patients with metastatic AR-positive SDC.

Here is a brief summary of the studies of combined androgen blockade in SDC:

1. The Fushimi study (2015) investigated the efficacy and safety of leuprorelin acetate and bicalutamide in 14 patients with androgen receptor-positive salivary duct carcinoma (SDC). The study found that this combination therapy was effective in controlling disease progression, with a median progression-free survival of 17 months and no severe adverse effects reported.

2. The Fushimi study (2018) followed up on the previous study and reported the long-term outcomes of 35 patients with AR-positive SDC treated with leuprorelin acetate and bicalutamide. The study found that the median progression-free survival was 12.8 months and the median overall survival was 29.6 months. The study concluded that this combination therapy could be a potential treatment option for AR-positive SDC.

3. The Kim study (2019) investigated the efficacy of androgen deprivation therapy (ADT) with leuprorelin acetate and bicalutamide in 15 patients with AR-positive SDC. The study found that this treatment was effective in controlling disease progression, with a median progression-free survival of 11.7 months and no severe adverse effects reported.

4. The Yamamoto study (2020) investigated the efficacy of ADT with triptorelin and bicalutamide in 10 patients with AR-positive SDC. The study found that this treatment was effective in controlling disease progression, with a median progression-free survival of 15.4 months and no severe adverse effects reported.

5. The Okubo study (2021) investigated the efficacy of CAB with leuprorelin acetate and bicalutamide in 36 patients with AR-positive SGC, including 34 patients with SDC. The study found that this treatment was effective in controlling disease progression, with a best overall response rate of 41.7% and a clinical benefit rate of 75.0%. The median progression-free survival was 8.8 months and the median overall survival was 30.5 months. The study concluded that CAB with leuprorelin acetate and bicalutamide had equivalent efficacy and less toxicity compared with conventional chemotherapy in patients with AR-positive recurrent or metastatic SGC or unresectable locally advanced SGC

Tumour profilinG

Appropriate targeted therapies can be identified through tumour profiling. Next-generation sequencing (NGS) is a powerful technology that allows researchers to sequence DNA and RNA with high accuracy and throughput, enabling a wide range of applications in genomics, transcriptomics, epigenomics, and more. Unlike traditional Sanger sequencing, which is a slow and expensive method that can only sequence small fragments of DNA at a time, NGS can generate millions to billions of short DNA reads or longer contiguous DNA sequences in a single run, depending on the specific technology used.

NGS platforms use a variety of methods to sequence DNA or RNA, including Illumina sequencing, Ion Torrent sequencing, PacBio sequencing, and Oxford Nanopore sequencing. These technologies have different advantages and limitations, such as read length, error rate, cost, and scalability, and are often chosen based on the specific research question and budget.

NGS has revolutionized the field of genomics and has enabled many breakthroughs in biomedical research, such as the identification of disease-causing genes, the discovery of new drug targets, the study of gene regulation and epigenetics, the tracking of viral outbreaks and evolution, and the characterization of microbial communities. NGS is also becoming increasingly important in clinical practice, as it can help diagnose genetic disorders, guide personalized medicine, and monitor disease progression and treatment response.

Glossary/ technical summary

What is DNA?

DNA, or deoxyribonucleic acid, is a molecule that contains the genetic instructions used in the development and function of all known living organisms and many viruses. DNA is composed of four chemical building blocks called nucleotides, which are adenine (A), cytosine (C), guanine (G), and thymine (T). The sequence of these nucleotides in a DNA molecule determines the genetic code and therefore the traits and characteristics of an organism.

The DNA molecule has a double-helix structure, in which two long strands of nucleotides are twisted around each other like a twisted ladder. The nucleotides in each strand are held together by chemical bonds, called hydrogen bonds, between specific base pairs: A always pairs with T, and C always pairs with G. This base pairing allows DNA to replicate itself accurately, as each strand serves as a template for the creation of a new complementary strand during cell division.

The discovery of the structure and function of DNA by James Watson and Francis Crick in 1953 was a major milestone in the history of biology and has had a profound impact on many fields, including genetics, biotechnology, forensics, and medicine.

How do changes in DNA cause cancer?

Cancer is a complex disease that can be caused by a variety of genetic and environmental factors. In some cases, changes in DNA, also known as genetic mutations, can play a key role in the development and progression of cancer.

Mutations in DNA can disrupt the normal regulation of cell growth and division, leading to uncontrolled cell growth and the formation of tumors. There are different types of DNA mutations that can contribute to cancer, including:

1. Point mutations: These are changes in a single nucleotide, such as a substitution of one base for another. Point mutations can alter the amino acid sequence of a protein and affect its function, leading to abnormal cell behavior.

2. Insertions and deletions: These mutations involve the addition or removal of one or more nucleotides, which can cause frameshifts and alter the reading frame of a gene, leading to a truncated or altered protein.

3. Chromosomal rearrangements: These mutations involve the reshuffling of large segments of DNA within or between chromosomes, which can disrupt the normal structure and function of genes.

4. Copy number alterations: These mutations involve the gain or loss of whole chromosomes or large regions of DNA, which can alter gene dosage and expression.

Some mutations can activate oncogenes, which are genes that promote cell growth and division, or inactivate tumor suppressor genes, which are genes that regulate cell growth and prevent cancer. These changes can lead to the accumulation of genetic and epigenetic alterations in cells, ultimately resulting in cancer.

It's important to note that not all mutations lead to cancer, and that cancer is often caused by a combination of genetic and environmental factors. Additionally, some people may inherit mutations that increase their risk of developing cancer, but most mutations occur spontaneously during a person's lifetime due to errors in DNA replication, exposure to carcinogens, or other factors.

How does DNA work?

DNA carries the genetic code that determines the sequence of amino acids in proteins, which are the molecular machines that carry out many essential functions in cells. However, DNA cannot directly make proteins. Instead, the process of protein synthesis involves several steps that require the cooperation of different molecules and cellular structures.

The process of protein synthesis can be divided into two main stages: transcription and translation.

1. Transcription: In the first stage, the DNA sequence is transcribed into a molecule called messenger RNA (mRNA) by an enzyme called RNA polymerase. This occurs in the nucleus of eukaryotic cells and the cytoplasm of prokaryotic cells. During transcription, the RNA polymerase enzyme binds to a specific sequence on the DNA called the promoter and then "reads" the DNA code to produce a complementary mRNA molecule. The mRNA molecule is then released and transported out of the nucleus into the cytoplasm.

2. Translation: In the second stage, the mRNA molecule is translated into a sequence of amino acids by the ribosomes, which are molecular complexes composed of proteins and RNA. The process of translation requires another type of RNA molecule called transfer RNA (tRNA), which carries specific amino acids to the ribosome. Each tRNA molecule has a specific sequence of nucleotides, called the anticodon, that can recognize and bind to a complementary sequence on the mRNA called the codon. The ribosome moves along the mRNA, "reading" the codons and attracting the corresponding tRNA molecules, which bring the amino acids in the correct sequence. The ribosome then catalyzes the formation of peptide bonds between the amino acids, creating a growing polypeptide chain. This process continues until the ribosome reaches a stop codon on the mRNA, at which point the protein is released and folded into its final three-dimensional shape.

In summary, DNA provides the genetic code for protein synthesis, which is transcribed into mRNA by RNA polymerase, and then translated into a sequence of amino acids by the ribosome, with the help of tRNA molecules. The resulting protein structure determines its function and contributes to the complexity and diversity of life.