Emerging Therapies in Liver Cancer Research

ABSTRACT

Even with the recent advances in the field of cancer research the treatment of  Liver cancer is a challenge to healthcare systems worldwide due to limited therapeutic options and poor clinical outcomes. This review provides a comprehensive overview of emerging therapies in liver cancer research by offering a panoramic view of immunotherapy, and biomarker-directed treatments. By understanding the essence of these recent important discoveries, this review aims to equip clinicians and researchers with insights for advancing the frontiers of liver cancer treatment and improving the prognosis for the patient.

KEYWORDS:

Liver cancer, Immunotherapy, Biomarker Discovery

INTRODUCTION

Liver cancer is one of the leading causes of cancer-related deaths worldwide and ranks sixth in prevalence globally. What makes it important and concerning is its steady rise in occurrence, unlike other top-ranking cancers. This increase is particularly striking in regions with high rates of liver diseases like hepatitis B and C emphasizing the urgent need for effective interventions[1]. Hepatocellular carcinoma (HCC) stands as the predominant form of primary liver cancer, constituting 75–85% of cases, while intrahepatic cholangiocarcinoma represents 10–15% of diagnoses.[2]. Over the past decade, immuno-oncology has reshaped the landscape of cancer treatment by offering novel therapeutic pathways. Immune checkpoints which are vital for maintaining self-tolerance are eventually taken over by tumours to evade immune surveillance. The arrival of immune checkpoint inhibition (ICI) therapies by utilizing monoclonal antibodies targeting PD-1/PD-L1 and CTLA-4, has marked a significant advancement in cancer treatment, yielding durable responses in a subset of patients[3]. Treatment for liver cancer depends on its type. HCC(hepatocellular carcinoma) can be treated with targeted drugs, immunotherapy and antiviral medicines, while ICC (intrahepatic cholangiocarcinoma) is usually treated with chemotherapy, targeted drugs and immunotherapy. Meanwhile, the Treatment for cHCC-ICC depends on how it looks under the microscope and genetic changes.[4] In this review, we will explore liver cancer research, including recent discoveries and innovative therapies. These advancements hold the potential to revolutionize the treatment and ultimately improve patients’ quality of life.

LITERATURE REVIEW

Understanding the Molecular Basis of Liver Cancer

Genetic studies have revealed a multitude of changes in the DNA of liver cancer cells, including mutations, deletions and amplifications. Liver cancer like hepatocellular carcinoma (HCC) often results from mutations in tumour suppressor genes disrupting their regulatory functions. Simultaneously, activation of oncogenes further promotes aberrant cell growth and proliferation culminating in tumour formation within the liver. Understanding the interplay between these genetic alterations is crucial for developing targeted therapies against HCC.[5]In a study conducted (Anabel Sanchez-Martin et al., 2023) researchers investigated how tumour suppressor genes influence liver cancer cells revealing their role in chemoresistance and disease severity. Mutations in TP53 or ARID1A and reduced CDKN1A expression were linked to poorer patient outcomes. By manipulating these genes in lab-grown liver cancer cells, researchers uncovered varied responses to anticancer drugs suggesting promising ways for personalized treatment approaches.[6] In another study (Krutsenko, Y., et al., 2021) researchers highlight the pivotal role of β-catenin in HCC development and progression. They explained how mutations in CTNNB1 and AXIN1 lead to β-catenin stabilization driving tumorigenesis. Targeting β-catenin particularly in subsets of HCC with these mutations emerges as a promising therapeutic strategy. Moreover, insights into β-catenin’s involvement in immune evasion and regulation of tumour metabolism through mTORC1 offer additional avenues for therapeutic intervention in HCC[7].

Immunotherapy Strategies in Hepatocellular Carcinoma

Immunotherapy has surfaced as a promising frontier in the treatment of hepatocellular carcinoma (HCC) by harnessing the body’s immune system against cancer[8]. A retrospective study (Cui, H et al.,2020) assessed the efficacy and safety of anti-PD-1 targeted therapy in advanced HCC patients treated with nivolumab or pembrolizumab. Results showed promising efficacy and mild toxicity, with longer survival in patients showing partial response or stable disease.[9] Another study (Park, D. J et al.,2021) investigated the expression of programmed death ligand 1 (PD-L1) in tumour-associated macrophages (TAMs) and its potential implications for HCC treatment. Co-culture experiments showed enhanced T cell functionality after blocking PD-L1 on M2 macrophages. In a mouse model, anti-PD-L1 treatment reduced tumour size and increased CD8+ T cell activation. The findings suggested that targeting PD-L1-expressing TAMs is a potential immunotherapeutic strategy for HCC[10] In another study (Bao, S et al.,2021), investigated the impact of the HCC microenvironment on tumour progression focusing on the immunosuppressive role of transforming growth factor-beta 1 (TGF-β1) on T cell function which revealed that TGF-β1 induces the upregulation of programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) in T cells, consequently impairing their cytotoxic activity against HCC cells alternate pathways for immunotherapeutic intervention in HCC by targeting TGF-β1 signalling [11].

Biomarker Discovery

Novel biomarkers like circulating nucleic acids (CNAs), Glypican-3 (GPC3) and SALL4 show promise for hepatocellular carcinoma (HCC) diagnosis and prognosis. CNAs offer non-invasive monitoring, while GPC3 and SALL4 present potential as specific HCC markers, aiding in accurate detection.[12] Cancer biomarkers including GPC3, SALL4 and circulating nucleic acids (CNAs) offer the potential for early diagnosis and treatment monitoring. These biomarkers enable targeted therapies such as GPC3-based CAR-T and guide precision medicine strategies. Emerging targets like FGFR4 and DDR1 show promise for enhancing treatment efficacy in liver cancer[13]. Biomarkers like AFU, GP73 and OPN offer the potential for early diagnosis of liver cancer although further validation is needed. Combined use of traditional biomarkers like AFP with novel ones enhances early detection accuracy. Signalling pathways like p53 and c-Met contribute to liver cancer progression. HSP70, GS, and GPC3 are valuable histological biomarkers aiding in accurate diagnosis while miRNAs like miR-122 show promise in distinguishing liver cancer from benign conditions.14]

CONCLUSION

Liver cancer treatment is evolving rapidly with advancements in targeted therapies, immunotherapy and biomarker-driven approaches. While significant progress has been made there are many challenges such as treatment resistance and access to care. Moving forward a multidisciplinary approach combined with continued research into combination therapies and therapeutics and early detection strategies would help improve outcomes for patients with liver cancer.

REFERENCES (APA)

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