Hepatocellular carcinoma (HCC) is swiftly increasing in prevalence globally with a
high mortality rate. The progression of HCC in patients is induced with advanced fibrosis,
mainly cirrhosis, and hepatitis. The absence of proper preventive or curative treatment
methods encouraged extensive research against HCC to develop new therapeutic strategies.
The Food and Drug Administration-approved Nexavar (sorafenib) is used in the treatment
of patients with unresectable HCC. In 2017, Stivarga (regorafenib) and Opdivo (nivolumab)
got approved for patients with HCC after being treated with sorafenib, and in 2018,
Lenvima (lenvatinib) got approved for patients with unresectable HCC. But, owing to
the rapid drug resistance development and toxicities, these treatment options are
not completely satisfactory. Therefore, there is an urgent need for new systemic combination
therapies that target different signaling mechanisms, thereby decreasing the prospect
of cancer cells developing resistance to treatment. In this review, HCC etiology and
new therapeutic strategies that include currently approved drugs and other potential
candidates of HCC such as Milciclib, palbociclib, galunisertib, ipafricept, and ramucirumab
are evaluated.