Checkpoint inhibition in hepatocellular carcinoma: Outsmarting the Squid Game.

The premise behind Squid Game, Netflix’s most viewed show to date, is a brutish contest where 456 bankrupted individuals risk their lives playing deadly children’s games for a chance to win an exorbitant money prize. The acclaimed series captures, on the silver screen, the plight of desperation and the willingness to sacrifice everything in the hopes for a cure to a bleak financial outlook. The show’s global success is perhaps attributable to its profound resonance with financial struggle, socio-economic disparities, and the quintessential tenets of human resilience. At its crux, Squid Game is a social commentary about survival, and the extreme lengths one may endure to not only live, but to prosper. Beyond a prima facie analysis, the Squid Game may indeed be an apt analogy for hepatocellular carcinoma (HCC) treatment. The first objective of any cancer treatment is, of course, to prolong survival. In the world of HCC, the ultimate Squid Game is its management. The brave player (ie, the patient diagnosed with advanced HCC beyond surgical cure) seeks to survive despite all odds—and is ready and willing to sacrifice everything to succeed. HCC therapy, therefore, is the Squid Game she must manoeuvre to survive, and her survival depends on the innovativeness of therapies to defeat HCC—its ability to grow, mutate and metastasize, and ultimately kill the host. Such survival strategies rival those employed by the players of the Squid Game, who seek innovative solutions to ensure livelihood. Analogous to the impact of direct active antivirals for hepatitis C treatment, immune checkpoint inhibitors (ICIs) have dramatically altered the landscape of oncology, and our fundamental understanding and approach to cancer treatment (1). ICIs thus allow the Squid Game player to potentially bypass the Front Man, thereby possibly Checkpoint inhibition in hepatocellular carcinoma