ARID1A Mutation and Potential Response to Immunotherapy for Cancer

Often when doctors determine if a patient may respond to standard immune checkpoint therapy, mainly meaning PD-1 inhibitors, Opdivo or Keytruda, they look at the PD-L1 status of the tumor. This is to see if the tumor has the receptor PD-L1, which correlates with blocking the corresponding receptor PD-1, removing one of the potential “brakes” of the immune system. We know, however that this is an imperfect marker; patients can respond with our without PD-L1 expression on the tumor, though generally, ones that do express PD-L1 would have a higher chance to respond. One study had even indicated that PD-L1 expression on the macrophage was more predictive than the tumor, but this is not what is used. In addition, looking at DNA repair genes, known as MMR, is another, though very rarely do patients have this. The other is tumor mutational burden. However,, we also know other gene mutations are associated with improved responses, but they are not used as selection criteria to give patients immunotherapy. This means that some patients who may respond are missing out. One of these described in a study published by Sarfatay, et al discusses a mutation in the gene ARID1A in cases of bladder cancer. We know it is probably any cancer, not just bladder. Patients with an ARID1A mutation may have a better chance to respond, and certainly should be considered for immunotherapy. Unfortunaltey, this still does not fit in the selection criteria for insurance coverage.

ARID1A is a gene that encodes a protein involved in regulating chromatin structure and gene expression. Chromatin is the complex of DNA and proteins that makes up the chromosomes inside the nucleus of cells, and its structure can impact how genes are expressed or repressed. ARID1A is often mutated or deleted in various types of cancer, including ovarian, endometrial, gastric, pancreatic, bladder, and liver cancer.

The loss of ARID1A function can lead to changes in gene expression, which can contribute to the development and progression of cancer. In particular, ARID1A mutations have been associated with alterations in DNA repair mechanisms, immune system regulation, and cellular metabolism, all of which can promote tumor growth and survival.

ARID1A mutations have also been studied as a potential biomarker for predicting response to specific cancer treatments, such as immune checkpoint inhibitors. Some studies have suggested that patients with ARID1A mutations may be more likely to respond to immunotherapy. However, more research is needed to confirm these findings and determine how they can be applied in clinical practice.

Overall, ARID1A is an important gene in cancer biology and is being studied as a potential therapeutic target and biomarker for various types of cancer.

Jason R. Williams, MD, DABR

Reference

Sarfaty M, Golkaram M, Funt SA, et al. Novel genetic subtypes of urothelial carcinoma with differential outcomes on immune checkpoint blockade. [published online ahead of print, 2023 Mar 16]. J Clin Oncol. Published online March 16, 2023. doi:10.1200/JCO.22.02144

https://www.cancernetwork.com/view/select-molecular-subgroups-may-predict-icb-responses-in-bladder-cancer

The post ARID1A Mutation and Potential Response to Immunotherapy for Cancer appeared first on Williams Cancer Institute.

source https://williamscancerinstitute.com/arid1a-mutation-and-potential-response-to-immunotherapy-for-cancer/?utm_source=rss&utm_medium=rss&utm_campaign=arid1a-mutation-and-potential-response-to-immunotherapy-for-cancer

Williams Cancer Institute

Tuesday, April 11, 2023