TEMA 1_ MOLECULAR PATHOGENESIS OF HCC

What is the incidence and expected number of liver cancer cases by 2025?

Liver cancer is currently the sixth most common cancer globally, with over 1 million cases expected in 2025.

What are the main risk factors for hepatocellular carcinoma (HCC)?

The main risk factors include HBV (54%), HCV (31%), alcohol (20%), NASH, and aflatoxin B1.

What is the significance of TERT promoter mutations in HCC?

TERT promoter mutations occur in 60% of HCCs and are considered critical gatekeepers in the progression of the disease.

What percentage of HCC cases develop in the setting of cirrhosis?

70-80% of patients develop HCC in the setting of cirrhosis.

How do mutations contribute to the oncogenesis of liver cancer?

Mutations in genes such as TERT, CTNNB1, TP53, and ALB are part of the landscape of mutations that drive the development of HCC.

What are the main signaling pathways disrupted in HCC?

Key disrupted signaling pathways in HCC include TGF-β, Wnt, Hedgehog, IGF, Raf/MAPK, EGFR, C-MET, and Akt/mTOR.

What is the role of immune classification in HCC treatment?

The immune classification helps identify 'hot tumours' that respond well to immunotherapy and can guide treatment strategies.

What was the first systemic treatment approved for HCC?

Sorafenib was the first systemic treatment approved for HCC.

How do combination therapies work in treating HCC?

Combination therapies aim to convert cold tumours into hot tumours to enhance the immune response and efficacy of immunotherapeutics.

What are the challenges in providing personalized medicine for HCC based on mutation analysis?

Only 25% of HCC tumors have actionable mutations, limiting options for targeted therapies.

Which tumors are considered to have a higher percentage of actionable mutations compared to HCC?

Biliary cancers have a higher percentage of actionable mutations (45%) compared to HCC, which has around 5%.

What is the expected growth in liver cancer incidence globally by 2025?

The incidence is expected to reach 1 million cases per year by 2025.

What is the role of VEGF inhibitors in HCC treatment strategies?

VEGF inhibitors can help transform cold tumors into hot tumors, facilitating a better response to immunotherapy.

How are T-cell exclusion mechanisms understood in the context of cold tumors?

Cold tumors often show oncogenic signaling that excludes T-cells, requiring a strategy to convert them into immune-active hot tumors.

Which immune class in HCC is characterized by higher immune infiltration?

The inflamed class, which shows a higher immune infiltration and a favorable anti-tumor immune composition.

What is a major limitation regarding the druggable mutations found in HCC?

Many of the most prevalent mutations in HCC are undruggable, posing a challenge for effective treatment.

What percentage of HCC tumors has at least one actionable target according to the recent analysis?

Only 25% of HCC tumors have at least one actionable target.

What are the common strategies for mutation testing in HCC?

Common strategies include identifying mutations, testing in vitro with cell lines, and in vivo testing using genetically engineered models.

What clinical trial result made Sorafenib the standard of care for HCC?

Sorafenib expanded survival from 8 months to 11 months compared to placebo.

How are FGF19 and cyclin D1 related to HCC tumorigenesis?

FGF19 and cyclin D1 genes drive tumor formation in HCC through high-level amplifications.