**Author details**

therapy (cytotoxic chemotherapy plus novel molecularly targeted therapy) versus sorafenib alone (the first-line therapy so far) for the management of patients with advanced unresectable HCC. Such studies should be addressed through large-sized randomized controlled phase II

Several genetic and epigenetics take place during hepatocarcinogenesis. These signaling pathways include the Wnt-b-catenin pathway, the hepatocyte growth factor/c-Met pathway, IGF and IGF-R pathways, and PI3 K/Akt/mTOR pathway. Several drugs targeting these significant pathways are currently undergoing early-stage assessment in patients with HCC

**•** Hepatocellular carcinoma (HCC) is a largely aggressive neoplasm that commonly takes

**•** At the time of clinical diagnosis, roughly 60%-70% of HCC patients present with primary advanced inoperable, recurrent, or metastatic disease [7]. Moreover, tumor relapse (recur‐ rence) following curative surgical management continues to be a substantial dilemma and

**•** Systemic therapy is the most appropriate choice for patients with primary advanced, inoperable, recurrent, or metastatic disease who were inappropriate candidates for other

**•** Systemic therapy is a rapidly developing area of research. Options of systemic therapy mainly include hormonal therapy, cytotoxic therapy, and novel molecularly targeted

**•** Single-agent tamoxifen or in combination with diverse chemotherapeutic drugs was unsatisfactory and failed to yield substantial worthy survival advantages. Similar discour‐ aging results occurred with megestrol administration as well as somatostatin analogs (octreotide and lanreotide). It can be concluded that the use of hormonal therapy for the management of advanced inoperable HCC is not recommended. Its use may be only

**•** HCC is largely a chemoresistant neoplasm [77]. The employment of systemic cytotoxic chemotherapy has been accompanied by low objective response rates, no survival advan‐ tages, and high frequencies of drug-related toxicities and adverse events. Moreover, there are no adequate data to endorse or approve any single-agent or combined chemotherapeutic cytotoxic regimens for the management of patients with advanced inoperable HCC [76].

**•** Systemic chemotherapy may still be regarded in patients whom their HCC get worse while on sorafenib and whom baseline liver function and performance status are adequate enough to endure it. The chemotherapy-related toxicities and adverse events should be carefully

is documented as high as approximately 70% at 5 years postoperatively [8].

and III trials; some of which are already ongoing.

130 Recent Advances in Liver Diseases and Surgery

**5. Summary and final remarks**

local or loco-regional therapies.

recommended in the context of clinical trials.

therapy.

place in the setting of chronic liver disease and cirrhosis.

[33, 133].

Ahmed Abu-Zaid1\*, Lynn Alkhatib1 , Judie Noemie Hoilat1 , Sana Samer Kadan1 , Abdulaziz Mohammed Eshaq1 , Ahmed Mubarak Fothan1 , Abdulrahman Mohammed Bakather1 , Mohammed Abuzaid2 , Daniah Saud Aloufi3 , Abdulhadi A. Alamodi4 and Ayman Azzam1,5,6

\*Address all correspondence to: aabuzaid@live.com

1 College of Medicine, Alfaisal University, Riyadh, Saudi Arabia

2 Faculty of Medicine, Khartoum University, Khartoum, Sudan

3 College of Medicine, Taiba University, Madinah, Saudi Arabia

4 University of Mississippi Medical Center, Jackson, Mississippi, United States of America

5 Faculty of Medicine, Alexandria University, Alexandria, Egypt

6 King Faisal Oncology Centre, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia

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