Colorectal Cancer

Conventional Treatments & Advanced Immunotherapy

Often treated synonymously, colon and colorectal cancers are among the most commonly diagnosed malignancies around the world. According to the American Cancer Society, 1 in 23 men and 1 in 26 women will develop colorectal cancer in their lifetimes.

The upside of its commonality is that many cases of colon cancer are highly treatable. If caught in its early stages, colon cancer has a five-year survival rate of 90.6%. Unfortunately, not all cases are caught early, and aggressive colon cancer types do exist. When this happens, patients often need to go beyond conventional surgery or chemotherapy interventions.

Immunotherapy for Colon and Colorectal Cancer

Colon cancers vs Colorectal Cancers

The human large intestine is made up of different segments, all containing largely the same type of tissue: the ascending, transverse, descending, and sigmoid colon. The rectum, on the other hand, is a smaller, slightly wider section between the sigmoid colon and the anus.

However, the rectum is made of the same type of muscles and tissues as the sigmoid colon. Their similarity and proximity mean that they are often affected by the same type of tumors. Moreover, cancers starting in the colon can often spread to the rectum, or vice-versa. As a result, many sources treat “colorectal cancers” as a single category.

Types of Colorectal Tumors

Most types of colorectal cancers belong to two types:

Colorectal adenocarcinomas

Adenocarcinomas are cancers that originate in the epithelial cells, which line up the inside of the colon. If left untreated, an adenocarcinoma of the sigmoid colon or rectum can spread into other layers of the colon, and eventually to other organs.

Mucinous adenocarcinomas

Accounting for up to 15% of all colorectal cancers, mucinous adenocarcinomas (MACs) also begin in the large intestine’s epithelial cells. However, this type of cancer also secretes mucus – a thinner tissue that can spread more quickly. This is why MACs often spread more quickly, and are deemed more aggressive.

Gastrointestinal carcinoid tumors

These tumors don’t start on the digestive tissue itself, but rather on the neuroendocrine cells attached to the colon. They generally grow slowly but cause no distinct symptoms. Instead, they are associated with weight loss, fatigue, bloating, and other “non-specific” problems, which can be difficult to diagnose. Approximately 1% of all colorectal cancers are carcinoid tumors.

Adenocarcinoma of the colon or rectum accounts for nearly 95% of all cases of colorectal cancer.

Rare types of colon cancer

In addition, rarer and more aggressive forms of colon cancer include:

  • Signet ring cell adenocarcinomas. This type of colorectal adenocarcinoma has a distinct cell shape: round, and denser on one side (like the gem on a signet ring). They grow very quickly and are more common among younger people.
  • Colorectal lymphomas. This type of cancer starts in the lymphocytes (white blood cells) that circulate around the large intestine. They are technically a type of non-Hodgkin lymphoma.
  • Gastrointestinal stromal tumors. This is a type of sarcoma that starts in the Interstitial Cells of Cajal, which line the G.I. tract. Although rare, they are often slow to grow but may cause chronic bleeding in the gastrointestinal tract.

Conventional Colorectal Cancer Treatments

Generally, the treatment for colon cancer will be determined by the type and stage in which it is first diagnosed.

The initial round of treatment will generally include surgery, followed by chemotherapy, radiotherapy, or both.

For early-stage (0 or I) adenocarcinomas, treatment often involves surgery alone. This may be a simple polypectomy (surgical extraction of the tumor in situ), or a more complex resection and anastomosis (that is, removing the compromised section of the bowel, and then sewing or stapling the remaining parts).

Chemotherapy for Colorectal Cancer

Once the malignant cells spread to other organs, surgery alone will not be enough. Therefore, for stage 3 or stage 4 colon cancer, the surgery will often be followed by chemotherapy. In some cases, doctors may try to shrink the tumor via chemotherapy first, and excise it afterwards.

Usually, chemotherapy is done as a combination regimen, where several drugs are used simultaneously to maximize their effects. Two of the most common protocols for chemotherapy for bowel cancer are:

  • FOLFOX (5-FU, leucovorin, and oxaliplatin)
  • CapeOx (capecitabine and oxaliplatin)

Chemotherapy is a very effective treatment for many types of cancer, but not all. If cancer cells prove to be resistant to chemotherapy, or if they have a high percentage of cancer stem cells, the repeated courses of chemotherapy are unlikely to provide any extra benefit. In these cases, a completely different approach is more likely to be effective than repeated chemo courses.

Many different chemotherapy protocols are currently in us for stage 4 colorectal cancer. However, at such an advanced stage, they are usually ineffective and will significantly worsen quality of life.

Radiation therapy for colorectal cancer

Radiotherapy is often given alongside chemotherapy, especially for metastatic colorectal carcinoma. In some cases, if the tumor is too large to remove, or is in a difficult location, radiotherapy may also be used to shrink a tumor before surgery.

Overall, radiation therapy is much more common when dealing with stage 3 or stage 4 colon cancer.  When dealing with aggressive colon cancer types, radiotherapy is used to destroy the tumor as much as possible.

In many cases, conventional treatments for metastatic colon carcinoma are successful, although they can be debilitating. In the event of a bowel cancer recurrence, however, their success rate drops significantly. In addition, following repeated surgeries and bowel resections, the impact on a patient’s quality of life multiplies.

Colorectal Cancer Immunotherapy

Immunotherapy is the use of a patient’s own immune system to fight against cancer cells. Over the past 10 years, immunotherapy has opened up new possibilities for patients with recurrent stage 4 colon cancer. Although there are different immunotherapy techniques and protocols in use, they all draw back from the same principle: they teach the immune system to recognize cancer cells as “foreign,” to attack them from the inside.

Even in metastatic cases, the colon cancer immunotherapy success rate may be promising. The response rates to established immunotherapy compounds can range from 40 to 78% for MMRd tumors, with exact outcomes dependent on the specific type of tumor.

At Biotherapy International, we are frequently creating and tweaking new types of immunotherapy for metastatic colon cancer. Our goal is to achieve minimal residual disease using traditional methods, followed by progressive immunotherapy. So far, the following advanced types of immunotherapy have been the most successful:

Oncolytic Viruses in Colorectal Cancer Treatment

Oncolytic viruses are special, patented viruses that are known to be harmless for humans, but that can attach themselves to cancer cells.

These viruses are often delivered intravenously or via injection, directly into a tumor, depending on the location. Once in the area, they can enter a tumor and start replicating inside. This process eventually triggers apoptosis or natural cell death. Then, the cell will release virions, which can infect adjacent tumor cells, while leaving healthy cells intact.

Each patient has their own history and prognosis. So far, we’ve seen patients for whom chemotherapy was not effective, but who responded very well to treatment with oncolytic viruses.

Colorectal cancer vaccines

Anti-cancer vaccines are a ground-breaking new method of colorectal cancer immunotherapy.

This vaccine uses modified cancer cells to “train” the immune system to recognize each patient’s specific cancer mutation. This triggers a potent and aggressive immune response, similar to the one triggered by an infection. 

To do this, we must first present the immune system with a slightly modified version of the cancer cell, mixed with an oncolytic virus or Coley’s toxin, that the immune system can recognize more easily. Therefore, developing these vaccines requires access to cryogenically-frozen samples of a patient’s own tumor tissue.

Adoptive cell therapy

This type of therapy uses a combination of intentionally mismatched “killer T cells” and monoclonal antibodies. This achieves two simultaneous effects:

  • It marks the antigens in cancer cells as “non-self”
  • It triggers a robust immune reaction, similar to that of organ rejection, but only against those cancer cells.

Often, this is  t done after an infusion of IL-2 cells, which also activates the patient’s own T cells and NK cells. 

Surviving colon cancer: New Solutions that Bring Renewed Hope

In best-case scenarios – that is, a simple adenocarcinoma caught early – colon cancer provides good survival rates. On the other hand, the five-year survival rate for signet ring cell adenocarcinoma is just 9%.

A patient’s quality of life following colon cancer will also depend on the amount and extent of surgeries performed. In recurrent cases, each subsequent resection chips away at the digestive system. This may leave patients with lifelong malabsorption problems or a permanent colostomy bag. Furthermore, unsuccessful courses of chemotherapy or radiotherapy also weaken the immune system and trigger systemic damage around the body.

Integrating new treatments for colon cancer, such as immunotherapy, will give the best chance to eradicate cancer down to the last malignant cell. In turn, this will maximize both quality of life and the chances of lifelong remission. As of today, experimental methods of immunotherapy for colon cancer provide the greatest chances for extending life and even achieving complete recovery.

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