Cridanimod Sensitization for Hormone-Refractory Cancer Therapy
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Solution Overview
Problem
Current treatments for primary progesterone receptor-negative (PR−) endometrial cancer and primary estrogen receptor-negative (ER−) breast cancer, particularly triple-negative breast cancer, are limited in effectiveness, with hormonal therapies showing low response rates due to lack of receptor expression and resistance to hormone therapies.
Innovation Solution
Administration of cridanimod or its salts/esters in combination with progesterone receptor agonists for PR− endometrial cancer and selective estrogen receptor modulators or down-regulators for ER− breast cancer to sensitize cancer cells, inducing receptor expression and enhancing treatment response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If hormonal therapy is administered to PR− endometrial cancer or ER− breast cancer patients, then treatment is provided, but response rate is low due to lack of receptor expression
Solution Approach 1:
The patent applies preliminary action by administering cridanimod before hormonal therapy to induce progesterone receptor expression in PR− endometrial cancer cells or estrogen receptor expression in ER− breast cancer cells. This preparatory step creates the necessary receptor expression that enables subsequent hormonal therapy to be effective, directly resolving the contradiction between treatment provision and low response rate due to lack of receptors
Solution Approach 2:
The patent applies parameter changes by using cridanimod to alter the biological state of cancer cells, specifically changing the expression levels of hormone receptors. This transformation converts PR− or ER− cancer cells into PR+ or ER+ cells, thereby changing the fundamental parameter of receptor expression that determines responsiveness to hormonal therapy
2Reliability
If progestin treatment is administered to induce cellular differentiation, then progesterone function is achieved, but PRs are depleted within target tissue
Solution Approach 1:
The patent applies preliminary action by using cridanimod to establish and maintain progesterone receptor expression before and during progestin treatment. This preliminary induction of PRs ensures that the target tissue has sufficient receptors to respond to progestin therapy, preventing the depletion problem that occurs with conventional treatment
Solution Approach 2:
The patent applies the intermediary principle by using cridanimod as a mediator that facilitates the interaction between progestin therapy and PR− cancer cells. Cridanimod acts as an intermediate agent that induces PR expression, enabling the progestin to effectively bind to and act on its receptors, thereby mediating the therapeutic effect in previously non-responsive cells
Data Source
AI summary
The invention provides a method for treatment of primary progesterone receptor-negative (PR−) endometrial cancer comprising administering (i) cridanimod or a salt or an ester thereof and (ii) a progesterone receptor (PR) agonist. The invention further provides a method for treatment of a primary estrogen receptor-negative (ER−) breast cancer, comprising administering (i) cridanimod or a salt or an ester thereof and (ii) a selective estrogen receptor modulator (SERM) or a selective estrogen receptor down-regulator (SERD). Also provided are compositions related to the above methods.