Since the mid-1970s, rates for liver cancer have been on the rise. A 2017 study found that liver cancer increased by 75 percent worldwide between 1990 and 2015, with the highest rate increases occurring in sub-Saharan Africa and Southeast Asia. Worldwide, hepatitis B—a virus that damages the liver and is spread through contact with infected blood and other body fluids—is the most common cause of liver cancer; however, in the United States, less than 5 percent of liver cancer cases stem from hepatitis B due to routine vaccination in children since the 1980s. In the United States, specifically, studies suggest that about 71 percent of liver cancer diagnoses can be attributed to preventable risk factors such as obesity, smoking, alcoholism. Despite the steady rise of liver cancer cases – and more than 700,000 deaths each year globally – there have been no significant advances in effective therapeutics in recent years to combat this dangerous disease.
Liver cancers are classified into two specific groups – primary and secondary. Primary liver cancer is when the cancer forms in the liver and is grouped into four different types based on the type of cells that become cancerous. Secondary liver cancer – also known as metastatic liver cancer – is when a cancer that forms in another part of the body, such as the stomach, breast, or colon, spreads to the liver. Metastatic liver tumors are the more common form of liver cancer in both the United States and Europe, while primary liver cancer tends to be more common in many areas of Asia and Africa.
To date, the 5-year survival rate for liver cancer ranges between 3 percent for those diagnosed with cancer that has spread to distant organs or tissues to 36 percent for individuals whose cancer has not spread beyond the liver. Although there have been many recent drug advancements for various other types of cancer, surgery is still the standard treatment for liver cancer due to the fact that liver cancer tumors do not respond well to most chemotherapy drugs. For this reason, there is an urgent need to create new, targeted treatments aimed at eliminating liver tumors and increasing the remission rate for those afflicted.
Monoclonal antibodies: a promising new approach
Monoclonal antibodies (mAbs) are manufactured proteins created to function like human antibodies within the immune system and are showing signs of becoming a promising new approach to treat liver cancer. Currently used to treat multiple cancers, such as breast and cervical cancer, mAbs are given to patients through an infusion and can be used alone or combined with other drugs. Compared to chemotherapy, mAbs are more precise in the way they attack cancer cells, with fewer normal cells being affected by the therapy. Depending on the antigen the mAb is targeting, it can work in a few different ways. Targeted therapies work by having an mAb bind directly to a cancer cell in order to kill it. This prevents the cancerous cell from multiplying, effectively stopping the cancer’s growth and drastically slowing down its overall progression.
Other mAbs – known as immunotherapies – help improve the immune system’s response to cancer cells. Immunotherapies work by acting on cells within the immune system and stimulating them to successfully block proteins that stop the immune system from attacking cancer cells. Additionally, mAbs can be modified to heighten their effectiveness. One of the most popular examples of this is the creation of bi-specific antibodies (BsAbs) – antibodies which engage two disease targets with one molecule.
Bi-specific antibodies show promise for the most common form of liver cancer.
As the monoclonal antibody market has continued to grow substantially, bi-specific antibodies have shown excellent pre-clinical and clinical results in a multitude of oncological clinical trials. To date, more than 180 BsAbs are in preclinical development and over 50 BsAbs have been investigated in clinical trials for solid tumors, including tumors associated with liver cancer.
Responsible for over 12,000 deaths per year in the United States, hepatocellular carcinoma (HCC), the most common form of primary liver cancer, has been the subject of many recent pre-clinical and clinical trials. Many innovative therapeutic options show promise against HCC, including bi-specific antibodies. In one recent preclinical study, a bispecific antibody proved effective in the prevention of HCC tumor growth with no adverse systemic effects. This bispecific antibody was more effective than other monotherapy treatments, suggesting that bispecific antibodies might be potential therapeutic treatments for HCC in the future.
For cancers with poor prognoses – such as HCC – ingenuity and innovation in the drug development process must continue to advance in order to improve overall outcomes and quality of life for patients. Fortunately, many pharmaceutical and biotech companies are putting a high priority on the creation of diverse treatment options and pushing the boundaries on what is possible in drug discovery. Because mAbs are still a relatively newer treatment option for cancers, they are still being investigated to determine both their overall effectiveness, as well as their potential drawbacks, such as the cost associated with their creation and potential adverse side effects.
As companies continue working to break new ground in the oncology space – from the creation of more targeted treatments to earlier detection methods – having an arsenal of diversified treatments means a greater chance to fight the disease from all fronts. We must ensure that new therapies, including mAbs, get the attention and resources they need as we continue to make strides toward our ultimate goal: winning the war on cancer.
Eugene Chan is a health care executive.