Neuregulin Antagonists Delay Tumor Recurrence

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Solution Overview

Problem

Current cancer treatments often fail to effectively target and prevent the recurrence of cancer, particularly in non-small cell lung cancer, due to the role of neuregulin autocrine signaling in tumor reinitiating cells, which survive chemotherapy and contribute to relapse.

Innovation Solution

Administering a neuregulin antagonist, such as an anti-NRG1 antibody, in combination with chemotherapeutic agents like paclitaxel and cisplatin, to inhibit neuregulin signaling and delay tumor recurrence in patients with various cancers, including non-small cell lung cancer and breast cancer.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If chemotherapy is administered to treat cancer, then initial tumor response is improved, but tumor recurrence and relapse occur

Engineering Contradiction:

Improveinitial tumor responseVSAvoidtime to tumor recurrence

Core Design Contradiction:

ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The patent applies preliminary action by targeting tumor reinitiating cells (TRICs) before they can cause recurrence. The neuregulin antagonist is administered to preemptively inhibit the signaling pathways that enable TRICs to survive chemotherapy and initiate relapse, thereby extending the duration of remission and delaying tumor recurrence

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent uses neuregulin antagonist as an intermediary substance that blocks the interaction between neuregulin and its receptor on TRICs. This intermediary agent interrupts the autocrine signaling loop that protects TRICs from chemotherapy, thereby preventing relapse without directly killing the cells

Inventive Principle:

Principle #24Intermediary (Mediator)

2Duration of action of stationary object

If neuregulin signaling is inhibited to prevent relapse, then time to tumor recurrence is improved, but understanding of TRIC biology is needed

Engineering Contradiction:

Improvetime to tumor recurrenceVSAvoididentification of TRICs

Core Design Contradiction:

Duration of action of stationary objectVSDifficulty of detecting and measuring

Solution Approach 1:

The patent applies self-service by utilizing the endogenous neuregulin signaling system itself as the target for therapy. The neuregulin antagonist exploits the fact that TRICs constitutively express high levels of neuregulin receptors and depend on autocrine neuregulin signaling for survival, making this pathway an ideal self-referential target for preventing relapse

Inventive Principle:

Principle #25Self-service

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The use of neuregulin antagonists significantly increases the time to tumor recurrence by inhibiting neuregulin-induced signaling, thereby enhancing the effectiveness of chemotherapy and preventing resistance in cancer treatment.

Implementation Method 1

The NRG antagonist may be an antibody, a small molecule, an immunoadhesin, or an RNA

Methodology Applied

Scientific EffectAntibody-antigen binding:

Data Source

PatentUS9556249B2Neuregulin antagonists and use thereof in treating cancer

Publication Date: 2017.01.31 GENENTECH INC

AI summary

The invention provides neuregulin antagonists and methods of using the neuregulin antagonists in delaying the time to tumor recurrence or preventing resistance of cancer cells to treatment with a therapeutic agent.