Therapeutic targeting of the pituitary tumor microenvironment

The tumor microenvironment (TME), the complex environment in which tumors develop, has been increasingly targeted for cancer treatment in recent years. Aggressive pituitary tumors and pituitary carcinomas have been so far targeted with immune-checkpoint inhibitors (28 cases, including a large cohort), and anti-angiogenic drugs (34 cases), specifically bevacizumab (30 cases), sunitinib (three cases), and apatinib (one case). Here, we re-viewed all these cases, reporting tumor response, potential predictors of response, as well as adverse events. Given that the histological type could potentially influence treatment response, we present the existing data separately for each type.Briefly, under ICIs, complete response was noted in one case, partial response in a third of cases, stable disease in 10% of cases, while 54% of tumors progressed. Under BVZ monotherapy, most cases (57%) showed stable disease, while 36% of tumors progressed; partial response was reported in only one case. The three cases treated with sunitinib monotherapy progressed. Regarding predictive factors of response, the tumor type (aggressive pituitary tumor versus pituitary carcinoma) appears as the strongest predictor of response to ICIs. To date, no predictor of response to anti-angiogenic drugs in the treatment of pituitary carcinomas and aggressive pituitary tumors has been identified. The interest of BZV add-on to first-or second-line chemotherapy warrants further investigation.In addition, we discuss perspectives regarding the TME-targeting in aggressive pituitary tumors and pituitary carcinomas, including perspectives on immunotherapy, anti-angiogenic drugs, as well as on other TME components, namely stromal cells, extracellular matrix, and secreted molecules.& COPY; 2023 Elsevier Inc. All rights reserved.

Automated summary

The complex tumor microenvironment (TME) has become an increasingly important target for cancer treatment. This study examined the use of immune-checkpoint inhibitors and anti-angiogenic drugs in treating aggressive pituitary tumors and pituitary carcinomas, reporting tumor response rates, potential predictors of response, and adverse events. The study found that the tumor type was the strongest predictor of response to immune-checkpoint inhibitors, while no predictors of response to anti-angiogenic drugs have been identified. The study also discussed the potential of TME-targeting strategies, including immunotherapy and targeting other TME components.