Combination therapy may help treat lung cancer - Medical News Today

• Lung cancer can be deadly and difficult to treat. Research into the development of new treatments is ongoing.
• Immunotherapy, or assisting the body's immune system in fighting cancer, is one treatment that is sometimes effective for people who have lung cancer.
• Results from a recent study found that combining a type of immunotherapy with a KRAS inhibitor may be effective in treating lung cancer but only in a specific subgroup of tumors.

Researchers have been working on developing treatment options to help increase the survival rates among people with lung cancer.

Now, a recent study published in the journal Science Advances reports that combining a specific KRAS inhibitor medication with immunotherapy may be an effective treatment for some people with lung cancer.

Lung cancer has a high mortality rate. Worldwide, lung cancer is the leading cause of cancer death.

The type of lung cancer will impact treatment options and strategies. One of the most common lung cancer types is non-small lung cell cancer (NSLCL).

Treatment options and plans will vary based on each person's unique needs. One option available is immunotherapy. Immunotherapy utilizes components of a person's immune system to fight off cancer. For example, immune checkpoint blockade (ICB) medications help the body better recognize and destroy cancer cells.

KRAS inhibitors are another available therapy option. Kirsten rat sarcoma (KRAS) is a specific gene and mutations in this gene can be found among people with lung cancer. Inhibiting this gene can help control cell growth and division and be a part of successful cancer treatment.

Researchers in the new study looked at combining KRAS inhibitors with immunotherapy as a more effective treatment option for lung cancer.

Researchers reviewed the effectiveness of the KRAS inhibitor KRAS^G12C using cancer cell lines and mouse models. Miriam Molina-Aracas, Ph.D., a study author and a principal laboratory research scientist at The Francis Crick Institute in London, noted the following highlights to Medical News Today:

"Treatment with KRAS^G12 in different pre-clinical lung cancer mouse models not only results in tumor shrinkage but also modifies the immune cells surrounding the tumor. We have identified different mechanisms by which oncogenic KRAS in the tumor cells can weaken the action of the immune cells that should recognize and kill the tumor cells. Inhibition of these mechanisms with the KRAS^G12C inhibitor reverses these detrimental effects and boosts again the immune response."

Researchers in this study further examined the combination treatment of KRAS^G12C and immune checkpoint blockade in lung cancer mouse models.

This combination therapy, they reported, was only effective in a particular subset of lung cancer tumors.

Researchers said the results indicate that this combination therapy will only be effective in a certain subset of people with lung cancer.

Dr. Molina-Arcas explained the type of tumors where the combo treatment was most effective:

In our study, we show that although the positive changes in the immune tumor microenvironment are observed in different models, only those tumors called "immune hot" (tumors that have active immune cells and have some response to immune checkpoint blockade) will benefit from the combination of KRASG12C inhibitors with immunotherapies.

The research of this study utilized mouse models, which only provide limited data.

Upal Basu Roy, Ph.D., MPH, the executive director of research at the LUNGevity Foundation in Chicago, was interested in the study's results and explained the following to MNT:

"When the researchers combined MTRX1257 [the KRAS inibitor] with approved drugs called immune checkpoint blockade (ICB) drugs, the effect of the ICB was increased by MRTX1257. This suggests that immune modulation by MRTX1257 can increase the efficacy of ICBs. Interestingly, the authors noted that this positive effect was not seen in all KRASG12C lung models they tested and only seemed to work in those tumors that were not intrinsically resistant to ICB, i.e., those tumors that did not show a response to ICB, to begin with."

As research moves forward, the focus will need to identify who could benefit from this combination therapy and also work to develop varied treatments where this combination is ineffective.

Molina-Acres explained to MNT:

"We are continuing to study how oncogenic KRAS can change the tumor microenvironment, especially in the tumors that do not respond to the combination of KRAS^G12C inhibitors with immunotherapies, with the objective to develop better combination strategies for this group of patients. We are also researching ways to stimulate the immune system to eliminate the cancer cells that have developed resistance to the KRAS^G12C inhibitors."

Overall, experts say the study provides hope for people with lung cancer that more individualized and effective treatments can be developed soon.