Why is the efficacy of new anti-cancer drugs limited?

One of the most common genetic mutations in various cancers is the KRAS mutation, but this type of mutation is generally considered "unable to be a drug

Including several other KRAS inhibitors, they all target the KRAS G12 mutation, which is also the most common mutation in lung cancer

These inhibitors can maintain oncoproteins in an inactive state, but only about 32%-37% of patients can respond, and the median progression-free period is about 6 months

A new study in Nature once again focused on this issue from the genetic level

They found that this resistance may come from several different molecular changes

By comparing tumor samples before and after treatment with sotorasib, the research team found that in the 27 resistant patients, many genes had additional mutations, including NRAS, BRAF, EGFR, and MYC, which have been found in a variety of cancer types Has a cancer-promoting effect

These gene mutations can make tumors detour when KRAS (G12C) is suppressed, restarting the tumor growth process

▲A variety of genes have been mutated after KRAS inhibitor treatment (picture source: reference [3])

From this result, the researchers speculate that there may be two situations.

In either case, cells with multiple genetic mutations can gain a huge survival advantage and take over the work after KRAS is blocked

Dr.

Now, there are some drugs that can target those additional cancer-promoting gene mutations, so the combination of these drugs and sotorasib will significantly increase the validity of the drug

They are currently conducting a phase 1 clinical trial of combined drug therapy

Note: The original text has been deleted

Reference materials:

[1] MSK Researchers Are Learning Why Some Patients Develop Resistance to'Landmark' Lung Cancer Drug.

[2] First Ever KRAS Inhibitor Approved for Non-Small Cell Lung Cancer.

[3] Zhao, Y.