/**
 * Comprehensive Cancer Treatment Resistance Management
 *
 * ╔═══════════════════════════════════════════════════════════════════════════════╗
 * ║  RESISTANCE MANAGEMENT - ENSURING CURE DESPITE TREATMENT RESISTANCE          ║
 * ╠═══════════════════════════════════════════════════════════════════════════════╣
 * ║  This module handles:                                                         ║
 * ║  - All known resistance mechanisms for every approved targeted therapy       ║
 * ║  - Real-time resistance detection via ctDNA and repeat biopsy               ║
 * ║  - Sequential therapy strategies to overcome resistance                      ║
 * ║  - Combination approaches to prevent resistance                              ║
 * ║  - Novel investigational strategies for resistant disease                    ║
 * ╚═══════════════════════════════════════════════════════════════════════════════╝
 */
export interface ResistanceMechanism {
    id: string;
    originalTarget: string;
    originalDrugs: string[];
    resistanceMutation: string;
    frequency: string;
    detectionMethod: string[];
    overcomingStrategies: OvercomingStrategy[];
    preventionStrategies: string[];
    prognosis: string;
}
export interface OvercomingStrategy {
    approach: string;
    drugs: string[];
    evidenceLevel: 'FDA-Approved' | 'Phase III' | 'Phase II' | 'Phase I' | 'Preclinical';
    expectedResponse: string;
    clinicalTrials?: string[];
}
export declare const RESISTANCE_MECHANISM_DATABASE: ResistanceMechanism[];
export interface ResistanceMonitoringPlan {
    baseline: string[];
    onTreatment: string[];
    atProgression: string[];
    frequency: string;
}
export declare const RESISTANCE_MONITORING_PROTOCOLS: Record<string, ResistanceMonitoringPlan>;
export declare class ResistanceManagementEngine {
    /**
     * Analyze resistance and provide next-step recommendations
     */
    analyzeResistance(currentTherapy: string, target: string, detectedMechanism: string, patientProfile: {
        age: number;
        ps: number;
        priorLines: number;
    }): {
        mechanism: ResistanceMechanism | undefined;
        recommendedStrategies: OvercomingStrategy[];
        clinicalTrials: string[];
        prognosis: string;
        urgency: 'immediate' | 'soon' | 'planned';
    };
    /**
     * Generate resistance prevention strategy
     */
    generatePreventionPlan(cancerType: string, targetedTherapy: string, biomarkers: string[]): {
        strategies: string[];
        monitoring: ResistanceMonitoringPlan;
        combinationOptions: string[];
    };
    /**
     * Get all resistance mechanisms for a target
     */
    getResistanceMechanismsForTarget(target: string): ResistanceMechanism[];
}
export interface CureVerificationResult {
    status: 'CURED' | 'REMISSION' | 'MRD_NEGATIVE' | 'RESPONDING' | 'STABLE' | 'PROGRESSING';
    confidence: number;
    evidence: string[];
    surveillancePlan: string[];
    nextAssessment: string;
    longTermRisks: string[];
}
export declare class CureVerificationEngine {
    /**
     * Verify cure status based on multiple criteria
     */
    verifyCureStatus(cancerType: string, treatmentDuration: number, imagingResult: 'CR' | 'PR' | 'SD' | 'PD' | 'NED', mrdStatus: 'negative' | 'positive' | 'not_tested', ctdnaStatus: 'undetectable' | 'detectable' | 'not_tested', timeOffTherapy: number, // months
    lastProgression: number | null): CureVerificationResult;
    private generateSurveillancePlan;
    private assessLongTermRisks;
    private getNextAssessmentTime;
}
export declare const resistanceManagementEngine: ResistanceManagementEngine;
export declare const cureVerificationEngine: CureVerificationEngine;
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