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25 January, 2024 by Anshul (neobio)
Liver Cancer at a Glance:
Each year, an increasing number of individuals are affected by HCC, making it a significant global health concern. As one of the most common and detrimental malignancies, HCC presents a unique set of challenges due to the limitations of traditional surgery and locoregional therapies.
Over the years, the importance of personalized and combination therapies in treating HCC has been brought to the forefront. This approach not only improves the survival rate of this devastating disease but also ushers in an important shift in its treatment strategy.
However, the landscape of liver cancer is further complicated by the rise of NASH, contributing to its onset. The connection between liver cancer and NASH underscores the need for a more comprehensive approach to preventing and treating this disease.
This article provides an overview of several emerging liver cancer drug targets, offering insight into the promising frontiers of targeted therapies in the fight against this global menace.
Targeted therapies have emerged as a potent weapon against cancer. These treatments work by targeting the specific cellular alterations that cause cancer, offering a more targeted approach compared to standard chemotherapy.
Targeted therapies are a type of cancer treatment that utilizes drugs to target specific genes and proteins involved in the growth and survival of cancer cells. Unlike chemotherapy, which affects all cells in the body, targeted therapies are designed to affect only cancer cells, thereby minimizing harm to healthy cells.
A significant part of targeted therapies in liver cancer treatment involves the use of kinase inhibitors. Kinases are proteins that carry crucial signals to the cell’s control center. In cancer cells, these proteins often contribute to tumor growth and progression. Kinase inhibitors, like Sorafenib and Lenvatinib, work by blocking these proteins, helping stop the growth of the cancer. These drugs are notably effective in treating advanced liver cancer, especially when other treatments are no longer helpful.
Another critical component of targeted therapies is the use of monoclonal antibodies. Monoclonal antibodies, such as Bevacizumab and Ramucirumab, inhibit angiogenesis, affecting a tumor’s ability to form new blood vessels, effectively starving the tumor of the resources it needs to grow.
The use of targeted therapies extends beyond kinase inhibitors and monoclonal antibodies. There is a growing interest in using combination therapies that pair targeted treatments with immune checkpoint inhibitors (ICIs). ICIs work by blocking proteins that prevent the immune system from attacking cancer cells. When used in conjunction with targeted therapies, they can enhance the effectiveness of treatment. For example, Bevacizumab has been used along with the ICI drug atezolizumab as a first-line treatment for liver cancer.
Advancements in understanding the molecular biology of liver cancer have paved the way for the development of targeted therapies. These treatments target specific molecular targets involved in the growth, proliferation and survival of cancer cells. The following are some key targets for liver cancer drugs that have been identified.
These drugs play a crucial role in liver cancer treatment, acting as kinase inhibitors. They block several kinase proteins that normally help tumor cells grow. Sorafenib is shown to work better in people with liver cancer caused by Hepatitis C, while Lenvatinib is taken once a day and used as the first treatment for liver cancer when surgery is not an option.
As mentioned above, Bevacizumab and Ramucirumab are monoclonal antibodies that impact tumor angiogenesis. Bevacizumab targets vascular endothelial growth factor (VEGF), a protein that aids new blood vessel formation. On the other hand, Ramucirumab targets VEGF receptor proteins on cells, attenuating new blood vessel formation.
β2-Spectrin, a protein that plays a crucial role in maintaining liver cell structure and function, is proposed as a potential drug target for liver cancer. It is especially important for preventing NASH, a liver disease that can lead to liver cancer.
The Hedgehog and Notch signaling pathways are involved in cellular growth, differentiation, and tissue morphogenesis. They are overactivated in many cancers, making them possible targets for liver cancer treatment.
These molecules play various roles in cellular proliferation, survival, and metabolism, which are processes often disrupted in cancer. They represent promising targets for new treatments for liver cancer.
Cancer stem cells (CSCs) are a small subset of cells within a tumor that can self-renew and produce the heterogeneous lineages of cancer cells that comprise the tumor. Targeting these cells is crucial because they are often resistant to conventional cancer treatments and are believed to be responsible for cancer recurrence.
Despite the significant advances in understanding and treating HCC, the disease remains a major healthcare challenge globally, and targeted therapies are not without complications. As such, focusing on the challenges and future directions in targeted therapy for liver cancer can provide a clearer roadmap towards effective treatment.
One of the key obstacles in targeted therapy for HCC is drug resistance, a common cause of treatment failure. This resistance is primarily due to the disease’s remarkable heterogeneity, exhibiting inter-patient, intertumoral, and intratumoral differences. These differences can significantly influence the response to various therapeutic agents, making the identification of useful biomarkers a complex task.
Additionally, adverse events related to drug use can complicate treatment. For example, patients are often switched between different therapeutic agents, like Sorafenib and Lenvatinib, when drug resistance develops. While it is unclear why this benefits some patients, it can potentially expose clinicians to criticism if serious adverse events occur.
Given the complexity of HCC, the identification and validation of reliable biomarkers have become increasingly critical in targeted therapy. Biomarkers can help predict the response to treatment, define suitable candidates for a particular targeted agent, and limit avoidable toxicity in patients unlikely to benefit.
Personalized treatment plans and multidisciplinary approaches show promise in managing HCC. Given the disease’s heterogeneity, personalized treatment plans can help tailor therapeutic strategies to individual patients, improving response rates. Additionally, a multidisciplinary approach, involving oncologists, hepatologists, and basic scientists, can help fully understand the mechanisms of HCC and ensure that the prognosis continues to improve.
The discovery of novel therapeutic compounds and biomarkers is crucial for the future of HCC management. New techniques, such as single-cell sequencing, liquid biopsy, and patient-derived cell lines, can aid in tracking the evolution of HCC. These advancements can help circumvent tumor heterogeneity, a significant challenge in the treatment of HCC.
At NeoBiotechnologies, we’re committed to advancing these efforts by manufacturing a variety of highly validated liver cancer-related monoclonal antibodies. These antibodies are ideal for various applications, including Immunohistochemistry, Flow Cytometry, Western Blotting, or Immunofluorescence, supporting researchers in their quest to improve HCC diagnosis and treatment.
