Kinin B₁ and B₂ Receptors: Role in Tumor Progression and Pain Associated With Tumor and Anticancer Therapy

Cancer is the second leading cause of death globally, with an estimated worldwide incidence of 19.3 million cases in 2020, and is expected to increase by 47% in the next 20 years. Painful symptoms of tumors and anticancer treatment negatively impact the quality of life of patients with cancer. Cancer pain can occur during all disease periods, being more debilitating and hardest to treat, mainly when tumors metastasize to the bone. Common tumors such as breast, lung, and prostate often metastasize to the bones and cause severe pain in patients. Anticancer therapy with some chemotherapy and hormonal drugs also induces painful symptoms, compromising antineoplastic treatment. Among the analgesics recommended to treat cancer pain, NSAIDs and paracetamol seem to have predominantly antiproliferative activity. However, opioids, mainly morphine, present conflicting effects in reducing and promoting tumor progression. Kinins and their B₁ and B₂ receptors contribute to the development of numerous painful symptoms,including those induced by tumors and anticancer therapy. In addition, kinins stimulate the proliferation of various tumors (breast, lung, prostate and others) while having controversial effects in melanoma. Thus, kinin B₁ and B₂ receptors could be a promising pharmacological target to treat the pain caused by the tumor and its therapy while reducing tumor proliferation. However, it is essential to review the effects of kinins in each specific type of cancer to investigate their involvement in pain. This assessment is also valid and prudent for new analgesic candidates against cancer pain and their therapy, especially to rule out a possible pro-tumor activity of this analgesic.