Esophageal cancer (EC) is cancer that occurs in the lining of the esophagus, a connection between the mouth and the stomach. It is usually of two types. The first one is adenocarcinoma, cancer that develops from gland cells at the base of the esophagus. It is the most prevalent form of esophageal cancer. Usually, it occurs near the stomach. Chances of getting adenocarcinoma are increased by the presence of persistent acid reflux, Barrett's esophagus, (a pre-cancerous condition), and chronic heartburn. The other one is squamous cell esophageal cancer which arises from the squamous cells lining the esophagus. It is associated with smoking and alcohol consumption, and organ transplants [1].
What is the treatment for EC?
The treatment of esophageal cancer depends on the etiology. Endoscopic mucosal resection and endoscopic sub mucosal dissection are common treatments for mucosal cancer, whereas esophagectomy is considered for locally advanced disease.
The transhiatal approach, the Ivor Lewis esophagectomy (right thoracotomy and laparotomy), and the McKeown technique (right thoracotomy followed by laparotomy and neck incision with cervical anastomosis) are the three most used methods for thoracic esophagectomy.
In many instances, a laryngectomy is required during surgery for cervical esophageal cancer.
For advanced cases, neoadjuvant chemotherapy or neoadjuvant chemo radiotherapy can be considered. The potential benefits of using chemotherapy are reduction of the severity of the tumor before surgery and a lesser chance of distant metastasis. Worldwide, 5-fluorouracil and cisplatin-based regimens are in use for EC.
The standard treatment for esophageal cancer where surgery is not possible is chemo radiotherapy, while it may also be considered for resectable tumors in some cases [2].
What is immunotherapy?
Immunotherapy is a form of cancer treatment that makes use of the patient's own body immune system. Immunotherapy can alter the immune system functioning to help it identify and fight against cancer cells. Immunotherapy has grown as an important component of various cancer treatments during the past few decades. Novel immunotherapies are being evaluated and approved, and the knowledge about the immune system functioning is expanding quickly. Immunotherapy is used to treat cancer in a variety of ways:
Checkpoint inhibitors: Immune system uses specific proteins called checkpoint proteins on immune cells, which operate as switches that must be switched on (or off) to initiate an immune response. These checkpoints are occasionally used by cancer cells to avoid immune system attacks. Immune checkpoint inhibitors are the drugs that focus on these checkpoint proteins in an effort to improve the immune system's defenses against different types of cancer cells.
Chimeric antigen receptor (CAR): This T-cell therapy involves removing a few T cells from patient’s blood, combining them with a unique virus that teaches the T cells how to adhere to tumor cells, and then infusing these T -cells back to the patient, where they identify, attach to, and fight against cancer cells..
Cytokines: This therapy stimulates the immune system to fight cancer by using cytokines, which are tiny proteins that transmit messages between cells.
Immunomodulators: This class of medications is used to treat specific types of cancer by enhancing various immune system components.
Vaccines: Vaccines are substances that are ingested to trigger an immune response in the body against specific diseases. Sometimes these vaccines are used to reduce or avoid cancer.
Monoclonal antibodies: These are synthetic copies of immune system proteins. Because they target a particular type of cancer cell, they are highly helpful in the treatment of cancer.
Oncolytic viruses: This therapy infects and destroys specific tumor cells by using viruses that have been altered in a lab [3].
How far is immunotherapy effective in EC?
Immune checkpoint inhibitors are effective in treating esophageal cancer. Pembrolizumab (keytruda), nivolumab (Opdivo), and ipilimumab (yervoy) are the prototype of these drugs that are proven to be effective in EC. The first two drugs target PD-1 (Programmed cell death) protein, whereas ipilimumab acts on CTLA-4 (cytotoxic T-lymphocyte antigen) present on T-cells. These proteins normally control T-cells from attacking cancer cells. By blocking this protein, these drugs help in the activation of the immune system and reduce the size of the tumor in esophageal cancer. This therapy is particularly useful in EC when other conventional treatments like surgery and radiotherapy failed. However, these drugs are associated with some atypical side effects like fatigue, cough, nausea, skin rashes, poor appetite, constipation, muscular or joint pain, itching, fever, and diarrhea and less frequently with more severe adverse effects like autoimmune reactions and infusion reactions [4].
Future outlook!
In patients with esophageal cancer, immune checkpoint inhibitors have shown some significant effect. But further efforts are required to lessen the undesirable adverse effects of these drugs in this disease. To evaluate the efficacy of these inhibitors in esophageal cancer with various mutational patterns, a larger clinical investigation is necessary.
References
1. “Esophageal Cancer - Introduction,” Cancer.Net, Jun. 25, 2012. https://www.cancer.net/cancer-types/esophageal-cancer/introduction (accessed Feb. 25, 2023).
2. H. Kato and M. Nakajima, “Treatments for esophageal cancer: a review,” Gen Thorac Cardiovasc Surg, vol. 61, no. 6, pp. 330–335, Jun. 2013, doi: 10.1007/s11748-013-0246-0.
3. “Treating Cancer with Immunotherapy | Types of Immunotherapy.” https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/what-is-immunotherapy.html (accessed Feb. 25, 2023).
4. “Esophageal Cancer Immunotherapy | Esophagus Cancer Immunotherapy.” https://www.cancer.org/cancer/esophagus-cancer/treating/immunotherapy.html (accessed Feb. 25, 2023).
