The Hedgehog protein (Hh) plays a critical role during a certain period of embryo development, but it normally has no role in adults except for the maintenance of adult stem cells. However, the Hedgehog protein has been detected in 70 percent of pancreatic cancer cell samples. As illustrated in the figures below, the Hedgehog protein binds to an integral membrane protein receptor known as Patched (Ptc), thus initiating a pathway of gene expression. When Hedgehog is absent, Ptc inhibits another protein known as Smoothened (Smo), which, in turn, blocks the activation of a group of proteins collectively known as the Hedgehog signaling complex (HSC). The inactivation is the result of proteolytic cleavage of one component of the HSC complex, a transcription factor known as Cubitus interruptus (Ci). When Hedgehog is present, it binds to Ptc, which prevents the inhibition of Smo by Ptc. The result is that Ci remains intact and can enter the nucleus, where it binds to and activates certain genes.

One approach to treating patients with pancreatic cancer and other cancers in which the Hedgehog protein is detected is to modify the Hedgehog signaling pathway. Which of the following is the most useful approach?

Treating patients with a molecule similar to Hedgehog would likely result in a similar signal transduction. Uncontrolled cell division would still occur in this case, leading to cancer.

Injecting patients with cells would not do much. Those cells would simply turn cancerous and spread if nothing was done to the signaling pathway.

A compound that can block Smo will terminate the signal transduction pathway. This would prevent cleavage of Ci and subsequent steps after.

Injecting patients with Ci to induce gene transcription would lead to uncontrolled cell division.