const pptxgen = require("pptxgenjs");

const pres = new pptxgen();
pres.layout = "LAYOUT_16x9";
pres.title = "Platinum Analogs in Cancer Therapy";
pres.author = "Cancer Therapeutics - Chapter 7";

// ─── COLOR PALETTE ───────────────────────────────────────────────────────────
const C = {
  darkBlue:  "0A1628",
  midBlue:   "1B3A6B",
  accent:    "00B4D8",
  gold:      "F4A261",
  light:     "E8F4FD",
  white:     "FFFFFF",
  gray:      "B0BEC5",
  darkGray:  "37474F",
  green:     "2ECC71",
  red:       "E74C3C",
  orange:    "F39C12",
  purple:    "9B59B6",
};

// ─── HELPERS ─────────────────────────────────────────────────────────────────
function addSlideHeader(slide, title, subtitle) {
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function addFooter(slide, num) {
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}

function colorBox(slide, x, y, w, h, color, text, textSize, textColor, bold) {
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}

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 1 – TITLE SLIDE
// ═══════════════════════════════════════════════════════════════════════════
{
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  s.addText("PLATINUM ANALOGS", {
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}

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 2 – TABLE OF CONTENTS
// ═══════════════════════════════════════════════════════════════════════════
{
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  addSlideHeader(s, "Table of Contents", "Chapter 7 – Platinum Analogs");

  const topics = [
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    ["02", "Platinum Chemistry", C.accent],
    ["03", "Approved Agents & Structures", "2196F3"],
    ["04", "Mechanism of Action", "8E24AA"],
    ["05", "Mechanisms of Resistance", C.red],
    ["06", "Combinatorial Strategies", C.green],
    ["07", "Clinical Pharmacology (PK/PD)", C.orange],
    ["08", "Pharmacogenomics", "00796B"],
  ];

  topics.forEach(([num, title, color], i) => {
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    const row = i % 4;
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      line: { color, width: 2 },
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      fontSize: 13, bold: true, color: C.darkGray, fontFace: "Calibri", valign: "middle",
    });
  });
  addFooter(s, 2);
}

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 3 – INTRODUCTION & HISTORY
// ═══════════════════════════════════════════════════════════════════════════
{
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    fill: { color: C.light }, line: { type: "none" },
  });
  addSlideHeader(s, "Introduction & History", "Discovery of Platinum Antitumor Activity");

  // Left column – intro text
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    x: 0.25, y: 0.95, w: 5.6, h: 3.8,
    fill: { color: C.white }, line: { color: C.accent, width: 1.5 },
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  s.addText([
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    { text: "Platinum drugs are a unique class of antitumor compounds. Cisplatin, carboplatin, and oxaliplatin have made a significant impact on treating solid tumors for 40+ years.\n\n", options: { fontSize: 11, color: C.darkGray } },
    { text: "Key Impact:\n", options: { bold: true, color: C.midBlue, fontSize: 13, breakLine: false } },
    { text: "• Curative in testicular & ovarian germ cell tumors\n• Prolongs survival in ovarian, lung, head & neck, bladder, and upper GI cancers\n• Spurred development of newer analogs and antiemetics", options: { fontSize: 11, color: C.darkGray } },
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    fontSize: 13, bold: true, color: C.accent, fontFace: "Calibri", align: "center",
  });

  const events = [
    ["1961", "Rosenberg discovers platinum antitumor activity"],
    ["1965", "Cis-isomer identified as active compound"],
    ["1978", "Cisplatin FDA approved"],
    ["1989", "Carboplatin approved (less toxic)"],
    ["2002", "Oxaliplatin approved (colorectal cancer)"],
    ["2009+", "Nedaplatin, Lobaplatin, Heptaplatin, Miriplatin"],
  ];
  events.forEach(([yr, ev], i) => {
    const y = 1.5 + i * 0.56;
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      fontSize: 9, color: C.white, fontFace: "Calibri", valign: "middle",
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  addFooter(s, 3);
}

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 4 – PLATINUM CHEMISTRY
// ═══════════════════════════════════════════════════════════════════════════
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    fill: { color: C.light }, line: { type: "none" },
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  addSlideHeader(s, "Platinum Chemistry", "Oxidation States, Geometry & Reactivity");

  // 3 chemistry concept cards
  const cards = [
    {
      title: "Oxidation States",
      color: C.midBlue,
      points: ["Pt exists in 2+ or 4+ state", "Pt(II) → square planar geometry", "Pt(IV) → octahedral geometry", "Stereochemistry critical for activity", "Trans-isomer has much less efficacy"],
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    {
      title: "Leaving vs Carrier Groups",
      color: "8E24AA",
      points: ["Ammine ligands = carrier groups (stable)", "Chloride/carboxylate = leaving groups", "Leaving groups displace to react with DNA", "Modifying leaving groups → different PK/tox", "Modifying carrier group → different activity spectrum"],
    },
    {
      title: "Aquation (Activation)",
      color: "00695C",
      points: ["Chloride replaced by water intracellularly", "Extracellular Cl⁻ (100 mEq/L) suppresses aquation", "Intracellular Cl⁻ (~10 mEq/L) allows aquation", "Mono- & di-aqua species formed", "Aquated Pt is the active electrophile"],
    },
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  cards.forEach((card, i) => {
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      x, y: 0.95, w: 3.1, h: 4.0,
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      line: { color: card.color, width: 2 },
      rectRadius: 0.12,
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      x, y: 0.95, w: 3.1, h: 0.48,
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    s.addText(card.title, {
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      fontSize: 12, bold: true, color: C.white, fontFace: "Calibri",
      align: "center", valign: "middle",
    });
    card.points.forEach((pt, j) => {
      s.addShape(pres.ShapeType.ellipse, {
        x: x + 0.18, y: 1.58 + j * 0.62, w: 0.12, h: 0.12,
        fill: { color: card.color }, line: { type: "none" },
      });
      s.addText(pt, {
        x: x + 0.36, y: 1.52 + j * 0.62, w: 2.6, h: 0.55,
        fontSize: 10, color: C.darkGray, fontFace: "Calibri", valign: "middle",
      });
    });
  });
  addFooter(s, 4);
}

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 5 – APPROVED AGENTS (with comparison chart)
// ═══════════════════════════════════════════════════════════════════════════
{
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  s.addShape(pres.ShapeType.rect, {
    x: 0, y: 0, w: "100%", h: "100%",
    fill: { color: C.light }, line: { type: "none" },
  });
  addSlideHeader(s, "Approved Platinum Agents", "Global & Regional Approvals");

  // Table header
  const cols = [1.8, 1.5, 2.0, 2.4, 1.5];
  const headers = ["Agent", "Approval", "Indication", "Key Feature", "DLT"];
  const colX = [0.15, 1.95, 3.45, 5.45, 7.85];
  s.addShape(pres.ShapeType.rect, {
    x: 0.15, y: 1.0, w: 9.7, h: 0.42,
    fill: { color: C.darkBlue }, line: { type: "none" },
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      x: colX[i] + 0.05, y: 1.0, w: cols[i], h: 0.42,
      fontSize: 11, bold: true, color: C.white, fontFace: "Calibri", valign: "middle",
    });
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    ["Cisplatin", "1978 (FDA)", "Testicular, ovarian, lung, H&N, bladder", "Broadest antitumor spectrum", "Nephrotoxicity"],
    ["Carboplatin", "1989 (FDA)", "Ovarian, NSCLC (often replaces cisplatin)", "Less renal/neuro tox; AUC-based dosing", "Myelosuppression"],
    ["Oxaliplatin", "2002 (FDA)", "Colorectal cancer (FOLFOX)", "Active in cisplatin-resistant CRC; DACH ligand", "Neurotoxicity"],
    ["Nedaplatin", "1995 (Japan)", "Lung, esophageal, H&N, bladder", "Higher water solubility; less renal tox", "Myelosuppression"],
    ["Lobaplatin", "2010 (China)", "CML, breast, SCLC", "Incomplete cross-resistance to cisplatin", "Thrombocytopenia"],
    ["Heptaplatin", "1999 (Korea)", "Gastric cancer", "Similar to cisplatin; bulkier structure", "Hepatotoxicity"],
    ["Miriplatin", "2009 (Japan)", "Hepatocellular carcinoma (TACE)", "Highly lipophilic; prolonged release", "Local effects"],
  ];
  const rowColors = ["FFFFFF", "EBF5FB", "FFFFFF", "EBF5FB", "FFFFFF", "EBF5FB", "FFFFFF"];
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    const y = 1.42 + i * 0.53;
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      x: 0.15, y, w: 9.7, h: 0.52,
      fill: { color: rowColors[i] }, line: { color: "D0D0D0", width: 0.5 },
    });
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    const agentColors = [C.midBlue, "8E24AA", "00695C", "1565C0", "6A1520", "E65100", "4A148C"];
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      s.addText(cell, {
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        fontSize: 9, color: C.darkGray, fontFace: "Calibri", valign: "middle",
      });
    });
  });
  addFooter(s, 5);
}

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 6 – MECHANISM OF ACTION
// ═══════════════════════════════════════════════════════════════════════════
{
  const s = pres.addSlide();
  s.addShape(pres.ShapeType.rect, {
    x: 0, y: 0, w: "100%", h: "100%",
    fill: { color: C.light }, line: { type: "none" },
  });
  addSlideHeader(s, "Mechanism of Action", "From Cell Entry to Apoptosis");

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  const steps = [
    { n: "1", title: "Cell Entry", body: "Via CTR1, VRAC (LRRC8D), OCT1/2 transporters. Simple diffusion also occurs. CTR1 degraded after substrate exposure.", color: C.midBlue },
    { n: "2", title: "Aquation", body: "Low intracellular Cl⁻ (~10 mEq/L) triggers mono/di-aqua species formation. Charged electrophile targets nucleophilic sites.", color: "8E24AA" },
    { n: "3", title: "DNA Adduct Formation", body: "Preferentially at N7 of guanine. GpG 1,2 intrastrand (65%), ApG 1,2 (25%), GpXpG 1,3 cross-links (~2%), interstrand G-G (~2%).", color: "00695C" },
    { n: "4", title: "DNA Damage Response", body: "ATM/ATR/DNA-PK activated. G2/M checkpoint arrest. NER attempts repair; MMR triggers futile cycles → apoptosis.", color: C.red },
    { n: "5", title: "Apoptosis", body: "p53 central decision-maker. Bcl-2 family, JNK, MAPK pathways involved. Immunogenic cell death (ICD) also triggered by oxaliplatin.", color: C.orange },
  ];

  steps.forEach((step, i) => {
    const x = 0.2 + i * 1.95;
    // card
    s.addShape(pres.ShapeType.roundRect, {
      x, y: 1.0, w: 1.85, h: 4.2,
      fill: { color: C.white },
      line: { color: step.color, width: 2 },
      rectRadius: 0.12,
    });
    // number circle
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      x: x + 0.6, y: 1.05, w: 0.65, h: 0.65,
      fill: { color: step.color }, line: { type: "none" },
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    s.addText(step.n, {
      x: x + 0.6, y: 1.05, w: 0.65, h: 0.65,
      fontSize: 18, bold: true, color: C.white, align: "center", valign: "middle", fontFace: "Calibri",
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    s.addText(step.title, {
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      fontSize: 11, bold: true, color: step.color, align: "center", fontFace: "Calibri",
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        x: x + 1.88, y: 2.35, w: 0.07, h: 0.22,
        fill: { color: C.gray }, line: { type: "none" },
      });
    }
  });
  addFooter(s, 6);
}

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 7 – DNA ADDUCTS (visual chart)
// ═══════════════════════════════════════════════════════════════════════════
{
  const s = pres.addSlide();
  s.addShape(pres.ShapeType.rect, {
    x: 0, y: 0, w: "100%", h: "100%",
    fill: { color: C.light }, line: { type: "none" },
  });
  addSlideHeader(s, "DNA Adduct Distribution", "Types of Platinum-DNA Lesions");

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  s.addText("Cisplatin DNA Adduct Types (% of total)", {
    x: 0.3, y: 0.95, w: 5.5, h: 0.35,
    fontSize: 13, bold: true, color: C.midBlue, fontFace: "Calibri",
  });

  const bars = [
    { label: "GpG 1,2 intrastrand", pct: 65, color: C.midBlue },
    { label: "ApG 1,2 intrastrand", pct: 25, color: C.accent },
    { label: "GpXpG 1,3 intrastrand", pct: 6, color: C.orange },
    { label: "Monofunctional adducts", pct: 2, color: C.green },
    { label: "Interstrand G-G", pct: 2, color: C.red },
  ];

  const maxW = 4.5;
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      x: 0.3, y, w: 2.5, h: 0.4,
      fontSize: 10, color: C.darkGray, fontFace: "Calibri", valign: "middle",
    });
    s.addShape(pres.ShapeType.rect, {
      x: 2.85, y: y + 0.06, w: maxW, h: 0.32,
      fill: { color: "DDDDDD" }, line: { type: "none" },
    });
    s.addShape(pres.ShapeType.roundRect, {
      x: 2.85, y: y + 0.06, w: barW, h: 0.32,
      fill: { color: bar.color }, line: { type: "none" }, rectRadius: 0.05,
    });
    s.addText(`${bar.pct}%`, {
      x: 2.85 + barW + 0.1, y, w: 0.5, h: 0.4,
      fontSize: 10, bold: true, color: bar.color, fontFace: "Calibri", valign: "middle",
    });
  });

  // Right panel – adduct differences
  s.addShape(pres.ShapeType.roundRect, {
    x: 5.5, y: 0.9, w: 4.2, h: 4.3,
    fill: { color: C.white },
    line: { color: C.midBlue, width: 1.5 },
    rectRadius: 0.12,
  });
  s.addText("Drug Differences in DNA Binding", {
    x: 5.6, y: 0.95, w: 4.0, h: 0.38,
    fontSize: 12, bold: true, color: C.midBlue, fontFace: "Calibri", align: "center",
  });

  const diffData = [
    ["Cisplatin", "GpG, ApG adducts; recognized by MMR → apoptosis", C.midBlue],
    ["Carboplatin", "Same adducts as cisplatin; 20-40x higher conc needed", "8E24AA"],
    ["Oxaliplatin", "Bulkier DACH-Pt adducts; NOT recognized by MMR; active in cisplatin-resistant CRC", "00695C"],
  ];
  diffData.forEach(([drug, desc, color], i) => {
    const y = 1.45 + i * 1.18;
    colorBox(s, 5.6, y, 1.3, 0.4, color, drug, 10, C.white);
    s.addText(desc, {
      x: 5.65, y: y + 0.45, w: 3.95, h: 0.62,
      fontSize: 9.5, color: C.darkGray, fontFace: "Calibri",
    });
  });
  addFooter(s, 7);
}

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 8 – MECHANISMS OF RESISTANCE
// ═══════════════════════════════════════════════════════════════════════════
{
  const s = pres.addSlide();
  s.addShape(pres.ShapeType.rect, {
    x: 0, y: 0, w: "100%", h: "100%",
    fill: { color: C.light }, line: { type: "none" },
  });
  addSlideHeader(s, "Mechanisms of Resistance", "Why Platinum Drugs Fail");

  const mechanisms = [
    {
      title: "Reduced Cell Entry",
      color: C.red,
      icon: "↓",
      points: ["LRRC8D deletion → cisplatin/carboplatin resistance", "CTR1 degraded by substrate → limits uptake", "AQP2/AQP9 downregulated in resistant lines"],
    },
    {
      title: "Increased Efflux",
      color: C.orange,
      icon: "↑",
      points: ["CTR2 overexpression → cisplatin efflux", "ATP7A/ATP7B (P-type ATPases) sequester/export platinum", "MRP2 (ABCC2) exports oxaliplatin"],
    },
    {
      title: "Drug Inactivation",
      color: "8E24AA",
      icon: "⊘",
      points: ["Glutathione (GSH) binds & inactivates platinum", "Metallothionein (MT) overexpression in resistant cells", "BSO (GSH depletion) only modestly restores sensitivity"],
    },
    {
      title: "Enhanced DNA Repair",
      color: C.midBlue,
      icon: "⚙",
      points: ["NER pathway (ERCC1/XPA/XPF) excises adducts", "High ERCC1 → cisplatin/oxaliplatin resistance", "BRCA1/2 mutations → initial sensitivity; secondary mutations → resistance"],
    },
    {
      title: "DNA Damage Tolerance",
      color: "00695C",
      icon: "✓",
      points: ["Translesion synthesis (TLS) by polymerase η", "Pol η bypasses oxaliplatin-GG adducts more easily", "Anti-apoptotic Bcl-2/Bcl-xL overexpression", "p53 mutation/loss → checkpoint disruption"],
    },
  ];

  mechanisms.forEach((mech, i) => {
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    const row = i < 3 ? i : i - 3;
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    const y = 1.0 + row * 1.5;
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  addFooter(s, 8);
}

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 9 – COMBINATORIAL STRATEGIES
// ═══════════════════════════════════════════════════════════════════════════
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      title: "Classic Cytotoxic Regimens",
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      items: [
        "BEP (Cisplatin + Bleomycin + Etoposide) → Testicular/germline",
        "FOLFOX (Oxaliplatin + 5-FU + Leucovorin) → Colorectal",
        "Carboplatin + Paclitaxel → Ovarian, NSCLC",
        "Cisplatin + Taxanes → Endometrial, H&N",
        "Carboplatin substituted for cisplatin in frail/elderly patients",
      ],
    },
    {
      title: "Platinum + DNA Repair Inhibitors",
      color: "8E24AA",
      items: [
        "PARP inhibitors: synergy via accumulation of DNA damage",
        "PARPi + Pt → increased myelosuppression (not yet approved combo)",
        "ATR inhibitors (CHK1 pathway): preclinical synergy",
        "ATRi + Carboplatin: only low ATRi doses tolerated in Phase I",
        "Multiple clinical trials underway",
      ],
    },
    {
      title: "Platinum + Immunotherapy",
      color: "00695C",
      items: [
        "Anti-PD1 + Platinum → lung, H&N, upper GI, TNBC (FDA approved)",
        "Platinum induces immunogenic cell death (ICD)",
        "↑ CD8+ T cells, ↓ Tregs, ↓ MDSCs in tumor microenvironment",
        "Pembrolizumab + Pemetrexed + Platinum: ORR 48% vs 20% (placebo)",
        "PFS 9.0 vs 4.9 months; OS 22.0 vs 10.6 months",
      ],
    },
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      x, y: 0.9, w: 3.12, h: 0.45,
      fill: { color: combo.color },
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      x: x + 0.05, y: 0.9, w: 3.02, h: 0.45,
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  addFooter(s, 9);
}

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 10 – PHARMACOKINETICS (with PK table as visual)
// ═══════════════════════════════════════════════════════════════════════════
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  addSlideHeader(s, "Clinical Pharmacokinetics", "Comparative PK of the 3 Main Platinum Agents");

  // PK comparison table
  const pkHeaders = ["Parameter", "Cisplatin", "Carboplatin", "Oxaliplatin"];
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    ["T½α (total Pt)", "14–49 min", "12–98 min", "26 min"],
    ["T½β (total Pt)", "0.7–4.6 h", "1.3–1.7 h", "—"],
    ["T½γ (terminal)", "24–127 h", "8.2–40 h", "38–47 h"],
    ["Protein binding", ">90%", "24–50%", "~85%"],
    ["Urinary excretion", "23–50%", "54–82%", ">50%"],
    ["Renal clearance", "OCT2-mediated", "GFR-correlated", "OCT2; less tubular accum."],
    ["Dosing basis", "mg/m²", "AUC (Calvert Eq.)", "mg/m²"],
    ["Nephrotoxicity", "High", "Low", "Low-moderate"],
    ["Neurotoxicity", "Moderate", "Low", "High (cumulative)"],
    ["Myelosuppression", "Moderate", "High (DLT)", "Moderate"],
  ];

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  const colX2 = [0.15, 2.55, 4.85, 7.15];
  const colW2 = [2.35, 2.25, 2.25, 2.6];

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        x: colX2[ci], y, w: colW2[ci], h: 0.4,
        fill: { color: ci === 0 ? "E8EAF6" : rowBg[ri] },
        line: { color: "D0D0D0", width: 0.5 },
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      s.addText(cell, {
        x: colX2[ci] + 0.05, y, w: colW2[ci] - 0.1, h: 0.4,
        fontSize: ci === 0 ? 10 : 9.5,
        bold: ci === 0,
        color: ci === 0 ? C.midBlue : C.darkGray,
        fontFace: "Calibri", valign: "middle",
      });
    });
  });
  addFooter(s, 10);
}

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 11 – CARBOPLATIN DOSING (Calvert Equation)
// ═══════════════════════════════════════════════════════════════════════════
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  addSlideHeader(s, "Carboplatin Dosing – Calvert Equation", "AUC-Guided Pharmacodynamic Dosing");

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    fontSize: 22, bold: true, color: C.accent, fontFace: "Calibri",
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    { title: "GFR Estimation", body: "CKD-EPI formula preferred\nNew eGFRcr(AS) formula (age + sex only)\nIsotopic EDTA clearance for accuracy", color: "8E24AA" },
    { title: "Why AUC Dosing?", body: "Carboplatin cleared by renal GFR\nHigh variability in clearance between patients\nAUC predicts platelet nadir and response", color: "00695C" },
    { title: "Platelet AUC Relationship", body: "Thrombocytopenia closely tied to AUC\nAllows individualized dosing\nAvoidsunder- & over-dosing", color: C.orange },
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      x, y: 2.35, w: 2.25, h: 0.42,
      fill: { color: card.color }, line: { type: "none" }, rectRadius: 0.12,
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      x: x + 0.05, y: 2.35, w: 2.15, h: 0.42,
      fontSize: 11, bold: true, color: C.white, fontFace: "Calibri", align: "center", valign: "middle",
    });
    s.addText(card.body, {
      x: x + 0.1, y: 2.85, w: 2.05, h: 2.28,
      fontSize: 10, color: C.darkGray, fontFace: "Calibri", valign: "top",
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  addFooter(s, 11);
}

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 12 – PHARMACOGENOMICS
// ═══════════════════════════════════════════════════════════════════════════
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  addSlideHeader(s, "Pharmacogenomics", "Genetic Predictors of Platinum Response & Toxicity");

  const pgData = [
    {
      topic: "ERCC1 SNPs (NER)",
      color: C.midBlue,
      detail: "rs11615 (C118T) & rs3212986 (C8092A) studied extensively. GWAS and meta-analyses do NOT support significant correlation. Not recommended as clinical biomarkers.",
    },
    {
      topic: "Cisplatin Ototoxicity",
      color: C.red,
      detail: "GWAS identified TPMT, COMT, ACYP2, WFS1 markers. Only rs316019 in SLC22A2 (OCT2) significantly associated in PanCareLIFE cohort (n=900). Clinical risk factors (age, radiation, cumulative dose) outperform genetic markers.",
    },
    {
      topic: "Cisplatin Nephrotoxicity",
      color: C.orange,
      detail: "Genes studied: SLC31A1 (CTR1), SLC22A2 (OCT2), ATP7A/B, SLC47A1 (MATE1), ABCB1, ABCG2, ABCC1-2. OCT2 variant rs316019 most consistently associated (systematic review). Same SNP linked to both oto- and nephrotoxicity.",
    },
    {
      topic: "BRCA1/2 & Sensitivity",
      color: "00695C",
      detail: "BRCA1/2 mutations highly predictive of primary platinum sensitivity. TC-NER dependent on BRCA1/2. Secondary BRCA mutations restoring WT reading frame mediate resistance in ovarian carcinoma.",
    },
    {
      topic: "Translesion Synthesis (Pol η)",
      color: "8E24AA",
      detail: "Pol η mRNA expression negatively correlates with cisplatin sensitivity in lung cancer lines. IHC positivity associated with poor benefit and shorter survival in metastatic gastric cancer (oxaliplatin-based Rx).",
    },
  ];

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}

// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 13 – TOXICITY COMPARISON (visual bar chart)
// ═══════════════════════════════════════════════════════════════════════════
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  addSlideHeader(s, "Toxicity Comparison", "Cisplatin vs Carboplatin vs Oxaliplatin");

  const toxData = [
    { tox: "Nephrotoxicity",    cis: 90, carb: 15, ox: 20 },
    { tox: "Neurotoxicity",     cis: 50, carb: 15, ox: 85 },
    { tox: "Ototoxicity",       cis: 70, carb: 15, ox: 10 },
    { tox: "Nausea/Vomiting",   cis: 95, carb: 40, ox: 50 },
    { tox: "Myelosuppression",  cis: 45, carb: 90, ox: 55 },
    { tox: "Hepatotoxicity",    cis: 20, carb: 10, ox: 15 },
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// ═══════════════════════════════════════════════════════════════════════════
// SLIDE 14 – SUMMARY & KEY TAKEAWAYS
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    { icon: "🎯", text: "Primary mechanism: formation of intrastrand DNA adducts (GpG 65%) → DNA damage response → apoptosis.", color: C.gold },
    { icon: "🔬", text: "Resistance arises from reduced uptake, enhanced efflux, GSH/MT inactivation, NER repair, and TLS bypass.", color: C.green },
    { icon: "💊", text: "Carboplatin uses AUC-based Calvert dosing (GFR + 25) to minimize myelosuppression variability.", color: "9B59B6" },
    { icon: "🤝", text: "Combination with immunotherapy (anti-PD1) dramatically improves outcomes in lung, H&N, and TNBC.", color: C.orange },
    { icon: "🧬", text: "BRCA1/2 mutations predict primary sensitivity; OCT2 SNP rs316019 associated with oto- and nephrotoxicity.", color: C.red },
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// ─── WRITE FILE ───────────────────────────────────────────────────────────────
pres.writeFile({ fileName: "/home/daytona/workspace/platinum-pptx/Platinum_Analogs_Cancer_Therapy.pptx" })
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