Inflammation is known to be a significant player in cancer progression. This study pinpointed that a high neutrophil-to-lymphocyte ratio (NLR) in the blood, which indicates peripheral blood myeloid expansion, is linked to shorter survival rates and treatment resistance across a variety of cancers and therapeutic approaches. However, the role of myeloid inflammation in prostate cancer progression has remained a grey area until this investigation.

The team discovered that a higher blood NLR mirrors an increase in tumour myeloid infiltration and tumour expression of certain molecules associated with myeloid chemoattracting. In a bid to ascertain whether myeloid cells contribute to resistance against androgen receptor signalling inhibitor (ARSI), and if blocking myeloid chemotaxis could reverse this, they carried out a clinical trial. They tested a combination of a CXCR2 inhibitor (AZD5069) and enzalutamide in patients with ARSI-resistant mCRPC.

The combination was well tolerated by the patients, without any dose-limiting toxicity. It led to a decrease in circulating neutrophils, reduced intratumour myeloid cell infiltration, and imparted durable clinical benefits with biochemical and radiological responses in a subset of mCRPC patients. This pioneering study provides the first clinical evidence that senescence-associated myeloid inflammation can fuel mCRPC progression and resistance to AR blockade. The findings suggest that targeting myeloid chemotaxis could be a viable strategy, meriting broader evaluation in other types of cancer as well.

This study brings a fresh perspective to the table, opening up avenues for further research in not only prostate cancer but potentially other cancers too, making strides towards a more optimistic future in cancer treatment advancements.