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Pancreatic ductal adenocarcinoma

Pancreatic cancer is the deadliest common cancer. Almost every tumour carries a KRAS mutation, and for the first time drugs against it are in pivotal trials.

Pancreatic ductal adenocarcinoma is defined by late presentation, a near-universal KRAS mutation (G12D ~40%, G12V ~30%, G12R ~15%, G12C ~1-2%; ~10% KRAS-wild-type with actionable fusions in NRG1, NTRK, ALK, or BRAF), a desmoplastic stroma that occupies most of the tumour, and an immunologically cold microenvironment. Surgery is the only cure and only ~20% of patients present resectable; five-year survival remains ~13% overall but exceeds 40% for resected patients who complete adjuvant mFOLFIRINOX.

For thirty years the story was chemotherapy: gemcitabine (1997), FOLFIRINOX (2011), gemcitabine/nab-paclitaxel (2013), adjuvant mFOLFIRINOX (PRODIGE 24, 2018), NALIRIFOX (2024), with olaparib maintenance for germline BRCA carriers (POLO, 2019) and zenocutuzumab for NRG1 fusions (2024) as the only biomarker-directed drugs. 2026 changed the trajectory. Optune Pax tumour treating fields were approved for locally advanced disease (PANOVA-3). Daraxonrasib, a pan-RAS(ON) inhibitor, nearly doubled overall survival in previously treated metastatic disease in RASolute 302 (13.2 vs 6.7 months, HR 0.40), presented in the ASCO 2026 plenary with simultaneous NEJM publication; regulatory filing is expected under a national priority voucher. The G12D-selective zoldonrasib, combined with daraxonrasib or with chemotherapy, produced response rates never before seen in this disease.

What remains unsolved: detection (no screening outside high-risk surveillance; MCED tests and new-onset-diabetes enrichment are the leading ideas), the stroma and immune exclusion that have defeated every checkpoint inhibitor trial, resistance to RAS inhibitors (already emerging), and the fact that half of patients are too frail for the most effective regimens. The most promising directions are RAS inhibitors moving into first line and neoadjuvant settings, personalised (autogene cevumeran) and shared-antigen (ELI-002 7P) vaccines in the adjuvant setting despite AMPLIFY-7P's miss, CLDN18.2 and FAP-directed delivery, and blood-based early detection.

State of the art today

  • First TTFields approval (2026).
  • Pan-RAS inhibitors with unprecedented OS in phase 1/2.
  • Personalised vaccines with durable immunity.
  • G12D-selective zoldonrasib combinations with 50% response rates in previously treated disease.
  • High-risk surveillance shifts ~3 in 4 detected cancers to stage I in carriers.
  • Personalised mRNA vaccine responders remain recurrence-free for years (autogene cevumeran phase 1).
Show survival figures (2)

Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.

  • RASolute 302 (2026): first targeted therapy to nearly double survival in pancreatic cancer; daraxonrasib heading for approval.
  • Adjuvant mFOLFIRINOX gives median OS beyond 4 years in resected fit patients.
Who it affects
Show survival figures (1)

Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.

  • Pancreatic cancer causes about 500,000 cases per year with 5-year survival of about 13%, and is projected to be the second-leading cancer killer in the US by 2030.

Where the cases are

Cases by country · GLOBOCAN 2022
All countries →

Site: Pancreas. World: 510,992 new cases, 467,409 deaths.

#CountryNew casesDeaths
1China118,672106,295
2United States of America60,12749,491
3Japan47,62743,265
4Germany21,86921,292
5Russian Federation21,84220,672
6France (metropolitan)15,89514,669
7Italy15,71014,903
8Brazil14,67014,294
9India13,66112,759
10United Kingdom11,35110,769

Standard of care

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Resectable/borderline

Neoadjuvant FOLFIRINOX → surgery → adjuvant chemotherapy.

NCCN Guidelines: Pancreatic Adenocarcinoma
Cytotoxic chemotherapyRobotic & minimally invasive surgery
Locally advanced

Chemotherapy ± TTFields (Optune Pax, 2026); SBRT or MR-guided RT; IRE in selected cases.

NCCN Guidelines: Pancreatic Adenocarcinoma
Optune / Optune Pax (TTFields)MR-guided adaptive radiotherapyIrreversible electroporation (NanoKnife)
Metastatic

FOLFIRINOX or gem/nab-pac; olaparib maintenance if gBRCA; zenocutuzumab if NRG1; trials of RAS inhibitors.

NCCN Guidelines: Pancreatic Adenocarcinoma
OlaparibZenocutuzumabDaraxonrasib
High-risk surveillance

Annual MRI/MRCP or EUS for germline carriers and familial kindreds (CAPS/PRECEDE); germline testing for every diagnosed patient and first-degree relatives.

High-risk pancreatic surveillance (CAPS / PRECEDE)Germline (hereditary) testingMRI
Resectable / borderline

Neoadjuvant mFOLFIRINOX (borderline; increasingly resectable), surgery, then adjuvant mFOLFIRINOX to complete ~6 months (PRODIGE 24); gemcitabine/capecitabine if unfit. Chemoradiation selectively (PREOPANC).

FOLFIRINOX / mFOLFIRINOXPRODIGE 24 / CCTG PA6PREOPANC-1 / PREOPANC-2Robotic & minimally invasive surgery
Locally advanced unresectable

FOLFIRINOX or gem/nab-paclitaxel; TTFields with gem/nab-paclitaxel (Optune Pax, 2026); SBRT or MR-guided ablative radiotherapy; IRE in selected centres; reassess for conversion surgery.

PANOVA-3Optune / Optune Pax (TTFields)Gemcitabine + nab-paclitaxelSBRT / SABR (stereotactic radiotherapy)
Metastatic, first line

mFOLFIRINOX or NALIRIFOX (fit) or gemcitabine/nab-paclitaxel; olaparib maintenance if gBRCA after ≥16 weeks platinum; zenocutuzumab if NRG1 fusion; pembrolizumab if MSI-H; trials of RAS inhibitors + chemotherapy.

NALIRIFOX (liposomal irinotecan + oxaliplatin + 5-FU/LV)NAPOLI 3POLOZoldonrasib
Metastatic, second line

Daraxonrasib once approved (RASolute 302: OS 13.2 vs 6.7 months) is expected to become the standard; otherwise switch backbone (gem/nab-pac after FOLFIRINOX, or liposomal irinotecan/5-FU after gemcitabine).

RASolute 302Daraxonrasib

Subtypes & biomarkers

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Subtypes
  • Classical (GATA6-high, better prognosis, more chemosensitive)
  • Basal-like / squamous (GATA6-low, poor prognosis)
  • KRAS-wild-type (~10%; NRG1, NTRK, ALK, BRAF fusions; MSI-H)
  • Germline-driven (BRCA2, PALB2, ATM, CDKN2A, STK11)
  • Pancreatic neuroendocrine tumours (a different disease; see neuroendocrine)
Biomarkers clinicians test
  • KRAS (G12D 40%, G12V 30%, G12R 15%, G12C 1-2%)
  • Germline BRCA/PALB2
  • MSI (rare)
  • NRG1 fusions (KRAS-wild-type)
  • CLDN18.2
  • CA19-9
  • CA 19-9 (prognosis and monitoring)
  • KRAS mutation subtype (G12D/V/R/C; wild-type triggers fusion testing)
  • Germline panel (BRCA1/2, PALB2, ATM, CDKN2A, STK11, Lynch)
  • HRD / platinum sensitivity
  • GATA6 (classical vs basal-like)
  • ctDNA (KRAS-mutant cfDNA) for MRD and response
  • FAPI PET avidity (investigational)
  • CLDN18.2 IHC (trials)

Target prevalence in this cancer

Target / alterationPrevalenceSource
FAP
Cancer-associated fibroblasts
>90%
Wikipedia
KRAS
G12D ~40%, G12V ~30%, G12R ~15%, G12C ~1-2%
85-90%
cBioPortal (TCGA)
Mesothelin
80-90%
Wikipedia
TP53
70-75%
cBioPortal (TCGA)
Tissue factor
50-80%
Wikipedia
TROP2
Approximate; heterogeneous
50%
PMC
Claudin 18.2
Wide range across series
20-60%
Wikipedia
PRMT5 (MTAP-deleted cancers)
20%
BRCA1 / BRCA2 (HRD)
5-8%
cBioPortal (TCGA)
PARP
5-8%
cBioPortal (TCGA)

How common each drug target or alteration is in this cancer. Population-level and approximate; see the target page for detail. Full matrix.

History

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  1. 1935Whipple describes pancreaticoduodenectomy

    Surgery becomes the only curative option, a status it still holds.

  2. 1982KRAS identified as a human oncogene

    Within a decade shown to be mutated in ~90% of pancreatic cancers.

    KRAS
  3. 1997Gemcitabine approved
  4. 1997Gemcitabine approved

    Clinical benefit response over 5-FU; the standard for 14 years.

    Gemcitabine + nab-paclitaxel
  5. 2011FOLFIRINOX improves survival
  6. 2011FOLFIRINOX: OS 11.1 vs 6.8 months

    PRODIGE 4 / ACCORD 11 establishes combination chemotherapy for fit patients.

    FOLFIRINOX / mFOLFIRINOX
  7. 2013Gemcitabine + nab-paclitaxel (MPACT)
    Gemcitabine + nab-paclitaxel
  8. 2018Adjuvant mFOLFIRINOX (PRODIGE 24)

    Median OS 54 months after resection.

    PRODIGE 24 / CCTG PA6
  9. 2019POLO: olaparib maintenance in gBRCA
    Olaparib
  10. 2019POLO: olaparib maintenance in gBRCA

    First biomarker-directed approval.

    POLOOlaparib
  11. 2021Sotorasib proves KRAS is druggable (G12C)

    Only 1-2% of pancreatic cancers carry G12C, but the door is open.

    Sotorasib
  12. 2023Autogene cevumeran phase 1 in Nature
    Autogene cevumeran
  13. 2023MRTX1133 regressions in G12D models; autogene cevumeran phase 1 in Nature
    MRTX1133Autogene cevumeran
  14. 2024NALIRIFOX approved; zenocutuzumab for NRG1 fusions
    NALIRIFOX (liposomal irinotecan + oxaliplatin + 5-FU/LV)Zenocutuzumab
  15. 2025PANOVA-3 positive; daraxonrasib phase 1/2 OS ~14.5 months
    PANOVA-3Daraxonrasib
  16. 2026Optune Pax approved; daraxonrasib phase 3 enrolled
    Optune / Optune Pax (TTFields)Daraxonrasib
  17. 2026RASolute 302: daraxonrasib OS 13.2 vs 6.7 months (HR 0.40)

    ASCO plenary and NEJM; Optune Pax approved; zoldonrasib combinations reported; AMPLIFY-7P vaccine misses.

    RASolute 302Optune / Optune Pax (TTFields)ZoldonrasibAMPLIFY-7P

Pipeline

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Under reviewSmall-molecule pan-RAS(ON) inhibitor
Daraxonrasib · Rasonque
Phase 2Personalised mRNA neoantigen vaccine
Autogene cevumeran
Phase 3ADC
Sonesitatug vedotin
Phase 2Theranostic pair (peptide radioligand)
FAP-2286 (177Lu / 68Ga)
Phase 3Multi-cancer early detection blood test
Galleri
Under reviewCAR-T (Claudin 18.2)
Satricabtagene autoleucel
Phase 2Small-molecule RAS(ON) G12D-selective inhibitor
Zoldonrasib
Phase 2Small-molecule RAS(ON) G12C-selective inhibitor
Elironrasib
Phase 1Small-molecule non-covalent KRAS G12D inhibitor
MRTX1133
Phase 2Off-the-shelf lymph-node-targeted KRAS peptide vaccine
ELI-002 7P
FAPI PETRASolute 302G12D-selective + pan-RAS(ON) inhibitor (zoldonrasib + daraxonrasib)High-risk pancreatic surveillance (CAPS / PRECEDE)PDAC organoid pharmacotypingRAS(ON) inhibitors to convert unresectable pancreatic cancer to resectableBlood-based pancreatic cancer detection in new-onset diabetesOff-the-shelf KRAS vaccines after pancreatic cancer surgeryFAP theranostics as a pan-cancer stromal strategyMRD / molecular residual disease testing

Open problems

  • Late diagnosis; no screening.
  • Dense stroma blocks drug delivery.
  • Immunologically cold.
  • Resistance to RAS(ON) inhibitors: secondary RAS mutations, RTK bypass, and adaptive feedback are already described; combination strategies are unproven in phase 3.
  • Half of patients are too frail for FOLFIRINOX-class regimens; RAS inhibitors may change this but toxicity (rash, stomatitis) is not trivial.
  • No population screening; MCED sensitivity for stage I PDAC is low and PPV in average-risk adults is poor.
  • Immune exclusion: every checkpoint inhibitor trial has failed outside MSI-H disease; vaccines must overcome a cold microenvironment.
  • Neoadjuvant versus upfront surgery for resectable disease remains unresolved after PREOPANC-2, NORPACT-1, and Alliance A021806.
  • Cachexia and biliary obstruction limit therapy delivery; supportive care is under-studied.
  • Access: RAS inhibitors and TTFields will be expensive; global disparities will widen.

Trials

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Recruiting now (live from ClinicalTrials.gov)

Recruiting trials near you · live from ClinicalTrials.gov
Pancreatic ductal adenocarcinoma
condition: pancreatic cancer
Open on ClinicalTrials.gov →

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Landmark trials in OnCo

AMPLIFY-7PLow-dose olanzapine for cancer anorexia (Tata Memorial)NAPOLI 3PANOVA-3POLOPonsegromab phase 2 in cancer cachexiaPREOPANC-1 / PREOPANC-2PRODIGE 24 / CCTG PA6RASolute 302

Expert centres

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Where the expertise is

Centres linked to this cancer in OnCo

Seeking a second opinion: ask your oncologist for a referral to a high-volume centre; most accept records and pathology by mail or telehealth. In the US, use the NCI's Find a Cancer Center tool or the nonprofit Cancer Commons, which navigates options for advanced cancers at no cost.

Questions to ask

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Bring to your appointment

Questions to ask your oncologist about Pancreatic ductal adenocarcinoma

Generated from this cancer's standard of care, biomarkers, and pipeline · 27 questions

Newly diagnosed

  1. What is my exact diagnosis, stage, and grade, and which tests established them?
    Why: Everything else follows from an accurate stage and subtype.
  2. Which biomarkers have been tested on my tumour (for example KRAS, Germline BRCA/PALB2, MSI, NRG1 fusions, CLDN18.2), and what were the results?
    Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
  3. Which subtype is my cancer, and does that change the recommended treatment?
    Why: Recognised subtypes for this cancer include Classical, Basal-like / squamous, KRAS-wild-type.
  4. Is germline (inherited) genetic testing recommended for me or my family?
    Why: Inherited variants can change treatment and matter for relatives.

Resectable/borderline

  1. For my situation (resectable/borderline), which of the standard options do you recommend and why?
    Why: Guideline options include: Neoadjuvant FOLFIRINOX → surgery → adjuvant chemotherapy.

Locally advanced

  1. For my situation (locally advanced), which of the standard options do you recommend and why?
    Why: Guideline options include: Chemotherapy ± TTFields (Optune Pax, 2026); SBRT or MR-guided RT; IRE in selected cases.
  2. Am I a candidate for Optune / Optune Pax (TTFields), and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Metastatic

  1. For my situation (metastatic), which of the standard options do you recommend and why?
    Why: Guideline options include: FOLFIRINOX or gem/nab-pac; olaparib maintenance if gBRCA; zenocutuzumab if NRG1; trials of RAS inhibitors.
  2. Am I a candidate for Olaparib, Zenocutuzumab, Daraxonrasib, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

High-risk surveillance

  1. For my situation (high-risk surveillance), which of the standard options do you recommend and why?
    Why: Guideline options include: Annual MRI/MRCP or EUS for germline carriers and familial kindreds (CAPS/PRECEDE); germline testing for every diagnosed patient and first-degree relatives.

Resectable / borderline

  1. For my situation (resectable / borderline), which of the standard options do you recommend and why?
    Why: Guideline options include: Neoadjuvant mFOLFIRINOX (borderline; increasingly resectable), surgery, then adjuvant mFOLFIRINOX to complete ~6 months (PRODIGE 24); gemcitabine/capecitabine if unfit. Chemoradiation selectively (PREOPANC).
  2. Am I a candidate for FOLFIRINOX / mFOLFIRINOX, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of PRODIGE 24 / CCTG PA6 and PREOPANC-1 / PREOPANC-2 apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Locally advanced unresectable

  1. For my situation (locally advanced unresectable), which of the standard options do you recommend and why?
    Why: Guideline options include: FOLFIRINOX or gem/nab-paclitaxel; TTFields with gem/nab-paclitaxel (Optune Pax, 2026); SBRT or MR-guided ablative radiotherapy; IRE in selected centres; reassess for conversion surgery.
  2. Am I a candidate for Optune / Optune Pax (TTFields), Gemcitabine + nab-paclitaxel, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of PANOVA-3 apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Metastatic, first line

  1. For my situation (metastatic, first line), which of the standard options do you recommend and why?
    Why: Guideline options include: mFOLFIRINOX or NALIRIFOX (fit) or gemcitabine/nab-paclitaxel; olaparib maintenance if gBRCA after ≥16 weeks platinum; zenocutuzumab if NRG1 fusion; pembrolizumab if MSI-H; trials of RAS inhibitors + chemotherapy.
  2. Am I a candidate for NALIRIFOX (liposomal irinotecan + oxaliplatin + 5-FU/LV), Zoldonrasib, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of NAPOLI 3 and POLO apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Metastatic, second line

  1. For my situation (metastatic, second line), which of the standard options do you recommend and why?
    Why: Guideline options include: Daraxonrasib once approved (RASolute 302: OS 13.2 vs 6.7 months) is expected to become the standard; otherwise switch backbone (gem/nab-pac after FOLFIRINOX, or liposomal irinotecan/5-FU after gemcitabine).
  2. Am I a candidate for Daraxonrasib, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of RASolute 302 apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Any stage

  1. Are there clinical trials I could join, for example of Daraxonrasib, Autogene cevumeran, Sonesitatug vedotin, FAP-2286 (177Lu / 68Ga)?
    Why: Trials are how the next standard of care is set; asking early keeps options open.
  2. Would a second opinion at a high-volume centre change anything, and can you help arrange it?
    Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
  3. What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?
    Why: Supportive care improves quality of life and helps patients complete treatment.
  4. I read that “Late diagnosis; no screening”. How does that affect my plan?
    Why: Open problems are where trials and second opinions matter most.
  5. I read that “Dense stroma blocks drug delivery”. How does that affect my plan?
    Why: Open problems are where trials and second opinions matter most.

Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.

Everything relevant

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Direct links plus the targets, companies, and technologies of this cancer's products.

technologies

54
Antibody-drug conjugate (ADC)Bariatric surgery and cancer incidenceBiliary stenting and drainageBispecific antibodiesCachexia pharmacotherapy: GDF-15 blockade, anamorelin, olanzapineCachexia-directed therapy (GDF-15 blockade)Cancer neuroscience: cutting the nerve supplyCancer-associated thrombosis prevention and treatmentCAR-T against stroma: fibroblasts and myeloid cellsCAR-T cell therapyCarbon-ion therapyCytotoxic chemotherapyDNA methylation profilingEarly integrated palliative careEngineered bacteria as living cancer drugsEngineered exosomes as drug carriersEnhanced recovery (ERAS) and perioperative nutritionEnteral and parenteral nutrition supportFAPI PETFocused ultrasound & histotripsyGermline (hereditary) testingGLP-1 receptor agonists and obesity-related cancer riskHigh-risk pancreatic surveillance (CAPS / PRECEDE)Hypoxia-activated prodrugsImmunonutrition before cancer surgeryIntraoperative radiotherapy (IORT)Intravesical therapy (BCG, chemotherapy, devices, gene and viral therapy)Irreversible electroporation (NanoKnife)KRAS & RAS inhibitorsLiquid biopsy (ctDNA)MR-guided adaptive radiotherapyMRD / molecular residual disease testingMRIMulti-cancer early detection (MCED)Nutrition support and cachexia managementOff-the-shelf cancer vaccinesOncology nutrition assessment and medical nutrition therapyPARP inhibitorsPDAC organoid pharmacotypingPersonalised neoantigen (mRNA) vaccinesPlatinum agentsPrehabilitation before cancer surgeryRadioligand therapy (beta emitters)Red and processed meat reductionResistance training and protein for cachexia and sarcopeniaRobotic & minimally invasive surgerySBRT / SABR (stereotactic radiotherapy)Small-molecule kinase inhibitorsTargeting the tumour's own microbesTargeting tumour mechanics and pressureTopoisomerase-I inhibitors (and ADC payloads)Tumour treating fields (TTFields)Ultra-processed food and sugar-sweetened drinksUltrasound

targets

17
BRCA1 / BRCA2 (HRD)CD73 / adenosine axisClaudin 18.2CSF1REGFREpCAMFAPHER2HER3KRASMesothelinMUC16 (CA-125)NTRKPARPPRMT5 (MTAP-deleted cancers)Tissue factorVISTA

drugs

25
Phase 2Personalised mRNA neoantigen vaccine
Autogene cevumeran
Under reviewSmall-molecule pan-RAS(ON) inhibitor
Daraxonrasib · Rasonque
Phase 2Off-the-shelf lymph-node-targeted KRAS peptide vaccine
ELI-002 7P
Phase 2Small-molecule RAS(ON) G12C-selective inhibitor
Elironrasib
Not mapped hereSmall-molecule EGFR TKI (first generation, reversible)
Erlotinib · Tarceva
Phase 2Theranostic pair (peptide radioligand)
FAP-2286 (177Lu / 68Ga)
Not mapped hereFluoropyrimidine antimetabolite
Fluorouracil (5-FU) · Adrucil / Efudex
Not mapped hereCytotoxic regimen
FOLFIRINOX / mFOLFIRINOX
Not mapped hereCytotoxic regimen
FOLFOX (5-FU, leucovorin, oxaliplatin)
Phase 3Multi-cancer early detection blood test
Galleri
Not mapped hereNucleoside analogue (deoxycytidine)
Gemcitabine · Gemzar / Infugem
Not mapped hereCytotoxic regimen
Gemcitabine + nab-paclitaxel · Gemzar + Abraxane
Not mapped hereTopoisomerase I inhibitor (camptothecin prodrug)
Irinotecan (and liposomal irinotecan) · Camptosar / Onivyde
Phase 1Small-molecule non-covalent KRAS G12D inhibitor
MRTX1133
ApprovedCytotoxic regimen
NALIRIFOX (liposomal irinotecan + oxaliplatin + 5-FU/LV) · Onivyde regimen
ApprovedSmall-molecule PARP inhibitor
Olaparib · Lynparza
Phase 3Small-molecule inhibitor (KRAS G12C)
Olomorasib
ApprovedDevice (tumour treating fields)
Optune / Optune Pax (TTFields) · Optune
Not mapped hereThird-generation platinum (DACH-platinum)
Oxaliplatin · Eloxatin
ApprovedCytotoxic chemotherapy (taxane)
Paclitaxel / nab-paclitaxel · Taxol / Abraxane
Under reviewCAR-T (Claudin 18.2)
Satricabtagene autoleucel
Phase 3ADC
Sonesitatug vedotin
ApprovedSmall-molecule inhibitor (KRAS G12C)
Sotorasib · Lumakras
ApprovedBispecific antibody (HER2×HER3)
Zenocutuzumab · Bizengri
Phase 2Small-molecule RAS(ON) G12D-selective inhibitor
Zoldonrasib

companies

23
AmgenAstellasAstraZenecaBioNTechBristol Myers SquibbCARsgen TherapeuticsEli Lilly (incl. Loxo)Elicio TherapeuticsFrontier MedicinesGRAILInsilico MedicineIpsenMerck & Co. (MSD)MerusNovartisNovocurePfizer (incl. Seagen)Quanta TherapeuticsRevolution MedicinesRoche / GenentechSanofiSOFIE BiosciencesVerastem Oncology

institutions

32
Australasian Gastro-Intestinal Trials GroupBarts Cancer Institute / Barts Health NHS TrustBeatson West of Scotland Cancer Centre / CRUK Scotland InstituteCedars-Sinai CancerCentro Nacional de Investigaciones Oncológicas (CNIO)Champalimaud Foundation – Champalimaud Clinical CentreCold Spring Harbor LaboratoryFred & Pamela Buffett Cancer CenterGarvan Institute of Medical Research / Kinghorn Cancer CentreGunma University Heavy Ion Medical CenterHolden Comprehensive Cancer Center, University of IowaINCLIVA Biomedical Research Institute / Hospital Clínico Universitario de ValenciaInstitut Paoli-CalmettesIRCCS Ospedale San RaffaeleLaura and Isaac Perlmutter Cancer Center at NYU Langone HealthLustgarten FoundationMayo Clinic Comprehensive Cancer Center – ArizonaMays Cancer Center at UT Health San AntonioNCT/UCC Dresden – University Hospital Carl Gustav CarusO'Neal Comprehensive Cancer Center at UABOntario Institute for Cancer ResearchPeking Union Medical College HospitalQST Hospital (National Institutes for Quantum Science and Technology)Ruijin Hospital, Shanghai Jiao Tong UniversitySalk Institute Cancer CenterSheba Medical CenterStand Up To CancerTianjin Medical University Cancer Institute and HospitalTUM Klinikum rechts der Isar / CCC MünchenUMC Utrecht Cancer CenterUniversity Cancer Center Mainz (UCT Mainz) / Universitätsmedizin MainzUZ Leuven / Leuven Cancer Institute

pathways

12
AutophagyCancer cachexiaCancer neuroscience (nerve–tumour signalling)DNA damage response & homologous recombinationDouble-strand break repair: HR versus end joiningEpithelial–mesenchymal transition & drug effluxFibroblast activation, desmoplasia & matrix stiffnessGlutamine addictionInvasion: proteases, adhesion & the invasive frontMicrobiome–tumour interactionsMYCRAS / RAF / MEK / ERK (MAPK)

terms

24
AdenocarcinomaAdenocarcinomaCA 19-9Cancer cachexiaDesmoplasia (tumour stroma)Downstaging and conversion therapyEndoscopy (EGD, EUS, ERCP)FOLFOX, FOLFIRI, FOLFIRINOX and CAPOXGermline BRCA mutation (gBRCA)Hazard ratio (HR)Hot vs cold tumoursKRAS mutation subtypes (G12C, G12D, G12V)Metabolic syndrome and insulin resistanceMinimal / molecular residual disease (MRD)Nutrition impact symptomsObesity-related cancers (IARC list of 13)Obstructive jaundice and biliary obstructionPerineural invasion (PNI)Peritoneum and peritoneal metastasesResectable, borderline resectable and unresectableRetroperitoneumStenting (biliary, oesophageal, airway)Tumour markerWhipple procedure (pancreaticoduodenectomy)

trials

9
AMPLIFY-7PLow-dose olanzapine for cancer anorexia (Tata Memorial)NAPOLI 3PANOVA-3POLOPonsegromab phase 2 in cancer cachexiaPREOPANC-1 / PREOPANC-2PRODIGE 24 / CCTG PA6RASolute 302

pairings

2
G12D-selective + pan-RAS(ON) inhibitor (zoldonrasib + daraxonrasib)Personalised neoantigen vaccine + PD-1 blockade

roadmaps

2
Early detection roadmap: organ screening → blood tests for many cancersKRAS roadmap: undruggable → G12C → pan-RAS

ideas

61
A billion-dollar prize for the first durable cure of a lethal metastatic cancerA blood test for the pre-metastatic nicheA dietitian in every gastrointestinal and head and neck tumour boardA guaranteed purchase prize for the first drug against a named hard targetA permanent neutral non-profit sponsor for multi-company platform trialsA perpetual platform trial in every major cancer, funded as infrastructureA ring-fenced metastasis programme with metastasis-specific endpointsA standing platform trial for every major cancer, funded as infrastructureA trial of GLP-1 weight-loss drugs with cancer as the primary outcomeAI that spots pancreatic cancer on scans taken a year before diagnosisAnchor a TGF-beta trap in the tumour stroma so it cannot act everywhereAutomatic germline testing for every cancer type where it changes careAutomatic palliative care referral triggered by diagnosis, not by declineBlock the complement signal that recruits tumour-protecting cellsBlood-based pancreatic cancer detection in new-onset diabetesBreak the neutrophil DNA nets that catch tumour cells after surgeryBurden-weighted portfolio targets for every major cancer funderCan MYC be drugged directly, and will patients tolerate it?Catch wasting early with a smart scale and a step counterClear the suppressive neutrophils out of pancreatic tumours firstCombine the new anti-wasting antibody with exercise and proteinCompeting sponsors share one control arm in the same indicationConfirm low-dose olanzapine for appetite and weight in advanced cancer worldwideCovalent chemistry for the RAS mutations that still have no drugCoverage-with-evidence registries for MR-guided and adaptive radiotherapyCure-focused prizes: pay for verified long-term cures, not for drugsCut the nerve supply to tumours with old drugsDe-acidify the tumour so T cells can work in itDedicated cohorts for patients with performance status 2 in first-line trialsEngineered bacteria that live in tumours and manufacture drugs thereEvery routine CT scan checked by AI for early cancer signs, with a tracked follow-up pathwayFAP theranostics as a pan-cancer stromal strategyFAPI PET as the workup for MCED positivesFour weeks of training and nutrition before major cancer surgery, as standardGet the one approved appetite drug licensed beyond a single countryGlucose monitor data as an early pancreatic cancer signalGrow each trial patient's tumour as organoids to decide which platform arm opens nextIn vivo CAR-T against solid-tumour antigensLink bariatric and GLP-1 registries to cancer registries in every country that has bothLosartan to loosen the stroma of pancreatic cancer before chemotherapy: a phase 3Make bespoke mouse cancer models in weeks with in vivo gene editingMake every cold tumour hot: a coordinated programme to reprogramme immune-excluded tumoursMatch therapy to the type of scar-forming cell in the tumourmRNA-delivered MYC decoy proteins instead of MYC inhibitorsNew diabetes after 50 plus weight loss triggers a pancreatic cancer checkOff-the-shelf KRAS vaccines after pancreatic cancer surgeryPartial lottery funding for good proposals in under-funded cancersPersonalised cancer vaccines at commodity cost through fully automated manufacturingPersonalised vaccines given only when the blood test turns positivePublic risk-adjusted outcome reporting for cancer surgery to drive centralisationRapid diagnostic centres for people with vague but worrying symptomsRAS(ON) inhibitors to convert unresectable pancreatic cancer to resectableReprogramme suppressive macrophages instead of trying to delete themSelect cachexia trial patients by the hormone driving their wastingShared concurrent control arms across sponsors' trials in the same settingSoften the tissue that new metastases need in order to growStop watching stable low-risk pancreatic cysts after five yearsTest DPYD, UGT1A1 and TPMT/NUDT15 before the first dose, everywhereTreat cachexia as a disease: GDF-15 blockade plus anabolic and nutrition bundlesTreat cachexia before it startsZebrafish avatars for a drug answer within a week

collections

1
Pancreatic Cancer Action Network (PanCAN)

people

27
Albert C. KoongAndrew J. AguirreAnirban MaitraBert VogelsteinCostas A. LyssiotisDavid A. TuvesonDo-Youn OhDung T. LeEileen M. O'ReillyElizabeth M. JaffeeFrank McCormickGiampaolo TortoraKevan M. ShokatLin ShenPeter J. O'DwyerPeter W. T. PistersPhilip D. GreenbergRaffit HassanRandy PauschRobert H. VonderheideSelwyn M. VickersSusan M. DomchekTanios Bekaii-SaabTheodore S. HongTheodore S. LawrenceTobias JanowitzVolker Heinemann

bottlenecks

11
Cachexia, toxicity and the limits of the patientCold tumours and the immunosuppressive microenvironmentFragmented care and guideline gapsFunding follows fashion, not burdenIncentives reward me-too drugs and marginal gainsInherited risk is mostly unidentifiedMost lethal cancers are found latePain relief and palliative care are unavailable to mostPreclinical models that do not predict peopleThe undruggable driversTumour heterogeneity and clonal evolution

key papers

6
Fifty years of the British Doctors Study: smokers lose ten years of life, quitting gives most of it backIARC verdict: excess body fat causes 13 cancersLe 2017: mismatch-repair deficiency predicts response to PD-1 blockade across twelve tumour types, leading to the first tissue-agnostic drug approvalNAPOLI-3: NALIRIFOX versus gemcitabine plus nab-paclitaxel as first treatment for metastatic pancreatic cancerOstrem and Shokat: the hidden pocket that made KRAS G12C druggableRojas 2023: a personalised mRNA vaccine trained T cells against each patient's pancreatic cancer, and those who responded stayed cancer-free longer

Key papers

6top
rctThe Lancet 2023changed practice
NAPOLI-3: NALIRIFOX versus gemcitabine plus nab-paclitaxel as first treatment for metastatic pancreatic cancer

For fit patients with newly diagnosed metastatic pancreatic cancer, a FOLFIRINOX-type regimen is now proven to be better than gemcitabine plus nab-paclitaxel, settling a long-standing debate. The absolute gain is about two months of median survival, and the regimen is more toxic for the gut. Whether liposomal irinotecan adds anything over conventional irinotecan (standard FOLFIRINOX) has never been tested head-to-head.

translationalNature 2023
Rojas 2023: a personalised mRNA vaccine trained T cells against each patient's pancreatic cancer, and those who responded stayed cancer-free longer

Pancreatic cancer was thought to be immunologically inert because of its low mutation burden; this study showed that with the right vaccine platform its few neoantigens can still be targeted. It is the strongest human evidence so far that personalised cancer vaccines can generate durable, tumour-specific immunity, and it justifies the randomised trials now running in pancreatic cancer and melanoma. Benefit is not yet proven, because responders may simply have had more immunogenic tumours.

translationalScience 2017changed practice
Le 2017: mismatch-repair deficiency predicts response to PD-1 blockade across twelve tumour types, leading to the first tissue-agnostic drug approval

This paper established a new regulatory paradigm: a drug approved for a molecular feature regardless of organ. It made MSI/MMR testing standard across advanced cancers and remains the clearest example of a biomarker that works across histologies. It also anchored the idea that mutation load, via neoantigens, is what makes tumours visible to T cells.

reviewNew England Journal of Medicine 2016changed practice
IARC verdict: excess body fat causes 13 cancers

Maintaining a healthy weight is now established cancer prevention for over a dozen cancer types. For clinicians and policymakers, obesity belongs alongside tobacco and alcohol in prevention strategy. Whether intentional weight loss in adulthood reverses risk is still being studied, including in trials of GLP-1 drugs.

basicNature 2013
Ostrem and Shokat: the hidden pocket that made KRAS G12C druggable

The most frequently mutated oncogene in cancer stopped being undruggable, and patients with KRAS G12C lung and bowel cancers now have targeted pills. The approach, exploiting a mutation-created chemical handle and an inactive-state pocket, has become a template for other hard targets.

observationalBMJ 2004changed practice
Fifty years of the British Doctors Study: smokers lose ten years of life, quitting gives most of it back

Smoking is the single largest preventable cause of cancer death, and quitting at any age helps, with the greatest gain from quitting young. Cessation support belongs in every cancer service, including lung screening programmes.

Latest papers

top
Literature trend2,619 papers in the last 12 months+24% vs prior 12How this is computed
Latest papers · live from Europe PMC
Open in Europe PMC

Query for this cancer: (TITLE:"Pancreatic ductal adenocarcinoma" OR ABSTRACT:"Pancreatic ductal adenocarcinoma") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Pancreatic ductal adenocarcinoma, not a curated reading list.

Connected

286top

Pages like this

not linked directly; found by shared links

technologies

46
Bariatric surgery and cancer incidenceBiliary stenting and drainageCachexia pharmacotherapy: GDF-15 blockade, anamorelin, olanzapineCachexia-directed therapy (GDF-15 blockade)Cancer neuroscience: cutting the nerve supplyCancer-associated thrombosis prevention and treatmentCAR-T against stroma: fibroblasts and myeloid cellsCAR-T cell therapyCarbon-ion therapyCytotoxic chemotherapyEarly integrated palliative careEngineered bacteria as living cancer drugsEngineered exosomes as drug carriersEnhanced recovery (ERAS) and perioperative nutritionEnteral and parenteral nutrition supportFAPI PETFocused ultrasound & histotripsyGermline (hereditary) testingGLP-1 receptor agonists and obesity-related cancer riskHigh-risk pancreatic surveillance (CAPS / PRECEDE)Hypoxia-activated prodrugsImmunonutrition before cancer surgeryIntraoperative radiotherapy (IORT)Irreversible electroporation (NanoKnife)KRAS & RAS inhibitorsLiquid biopsy (ctDNA)MR-guided adaptive radiotherapyMRD / molecular residual disease testingMRIMulti-cancer early detection (MCED)Nutrition support and cachexia managementOff-the-shelf cancer vaccinesOncology nutrition assessment and medical nutrition therapyPARP inhibitorsPDAC organoid pharmacotypingPersonalised neoantigen (mRNA) vaccinesPrehabilitation before cancer surgeryRed and processed meat reductionResistance training and protein for cachexia and sarcopeniaRobotic & minimally invasive surgerySBRT / SABR (stereotactic radiotherapy)Targeting the tumour's own microbesTargeting tumour mechanics and pressureTumour treating fields (TTFields)Ultra-processed food and sugar-sweetened drinksUltrasound

targets

15
BRCA1 / BRCA2 (HRD)CD73 / adenosine axisClaudin 18.2CSF1REpCAMFAPHER3KRASMesothelinMUC16 (CA-125)NTRKPARPPRMT5 (MTAP-deleted cancers)Tissue factorVISTA

drugs

25
Phase 2Personalised mRNA neoantigen vaccine
Autogene cevumeran
Under reviewSmall-molecule pan-RAS(ON) inhibitor
Daraxonrasib · Rasonque
Phase 2Off-the-shelf lymph-node-targeted KRAS peptide vaccine
ELI-002 7P
Phase 2Small-molecule RAS(ON) G12C-selective inhibitor
Elironrasib
Not mapped hereSmall-molecule EGFR TKI (first generation, reversible)
Erlotinib · Tarceva
Phase 2Theranostic pair (peptide radioligand)
FAP-2286 (177Lu / 68Ga)
Not mapped hereFluoropyrimidine antimetabolite
Fluorouracil (5-FU) · Adrucil / Efudex
Not mapped hereCytotoxic regimen
FOLFIRINOX / mFOLFIRINOX
Not mapped hereCytotoxic regimen
FOLFOX (5-FU, leucovorin, oxaliplatin)
Phase 3Multi-cancer early detection blood test
Galleri
Not mapped hereNucleoside analogue (deoxycytidine)
Gemcitabine · Gemzar / Infugem
Not mapped hereCytotoxic regimen
Gemcitabine + nab-paclitaxel · Gemzar + Abraxane
Not mapped hereTopoisomerase I inhibitor (camptothecin prodrug)
Irinotecan (and liposomal irinotecan) · Camptosar / Onivyde
Phase 1Small-molecule non-covalent KRAS G12D inhibitor
MRTX1133
ApprovedCytotoxic regimen
NALIRIFOX (liposomal irinotecan + oxaliplatin + 5-FU/LV) · Onivyde regimen
ApprovedSmall-molecule PARP inhibitor
Olaparib · Lynparza
Phase 3Small-molecule inhibitor (KRAS G12C)
Olomorasib
ApprovedDevice (tumour treating fields)
Optune / Optune Pax (TTFields) · Optune
Not mapped hereThird-generation platinum (DACH-platinum)
Oxaliplatin · Eloxatin
ApprovedCytotoxic chemotherapy (taxane)
Paclitaxel / nab-paclitaxel · Taxol / Abraxane
Under reviewCAR-T (Claudin 18.2)
Satricabtagene autoleucel
Phase 3ADC
Sonesitatug vedotin
ApprovedSmall-molecule inhibitor (KRAS G12C)
Sotorasib · Lumakras
ApprovedBispecific antibody (HER2×HER3)
Zenocutuzumab · Bizengri
Phase 2Small-molecule RAS(ON) G12D-selective inhibitor
Zoldonrasib

companies

13
AstraZenecaBioNTechBristol Myers SquibbCARsgen TherapeuticsElicio TherapeuticsFrontier MedicinesInsilico MedicineIpsenNovocureQuanta TherapeuticsRevolution MedicinesSOFIE BiosciencesVerastem Oncology

institutions

32
Australasian Gastro-Intestinal Trials GroupBarts Cancer Institute / Barts Health NHS TrustBeatson West of Scotland Cancer Centre / CRUK Scotland InstituteCedars-Sinai CancerCentro Nacional de Investigaciones Oncológicas (CNIO)Champalimaud Foundation – Champalimaud Clinical CentreCold Spring Harbor LaboratoryFred & Pamela Buffett Cancer CenterGarvan Institute of Medical Research / Kinghorn Cancer CentreGunma University Heavy Ion Medical CenterHolden Comprehensive Cancer Center, University of IowaINCLIVA Biomedical Research Institute / Hospital Clínico Universitario de ValenciaInstitut Paoli-CalmettesIRCCS Ospedale San RaffaeleLaura and Isaac Perlmutter Cancer Center at NYU Langone HealthLustgarten FoundationMayo Clinic Comprehensive Cancer Center – ArizonaMays Cancer Center at UT Health San AntonioNCT/UCC Dresden – University Hospital Carl Gustav CarusO'Neal Comprehensive Cancer Center at UABOntario Institute for Cancer ResearchPeking Union Medical College HospitalQST Hospital (National Institutes for Quantum Science and Technology)Ruijin Hospital, Shanghai Jiao Tong UniversitySalk Institute Cancer CenterSheba Medical CenterStand Up To CancerTianjin Medical University Cancer Institute and HospitalTUM Klinikum rechts der Isar / CCC MünchenUMC Utrecht Cancer CenterUniversity Cancer Center Mainz (UCT Mainz) / Universitätsmedizin MainzUZ Leuven / Leuven Cancer Institute

pathways

12
AutophagyCancer cachexiaCancer neuroscience (nerve–tumour signalling)DNA damage response & homologous recombinationDouble-strand break repair: HR versus end joiningEpithelial–mesenchymal transition & drug effluxFibroblast activation, desmoplasia & matrix stiffnessGlutamine addictionInvasion: proteases, adhesion & the invasive frontMicrobiome–tumour interactionsMYCRAS / RAF / MEK / ERK (MAPK)

terms

24
AdenocarcinomaAdenocarcinomaCA 19-9Cancer cachexiaDesmoplasia (tumour stroma)Downstaging and conversion therapyEndoscopy (EGD, EUS, ERCP)FOLFOX, FOLFIRI, FOLFIRINOX and CAPOXGermline BRCA mutation (gBRCA)Hazard ratio (HR)Hot vs cold tumoursKRAS mutation subtypes (G12C, G12D, G12V)Metabolic syndrome and insulin resistanceMinimal / molecular residual disease (MRD)Nutrition impact symptomsObesity-related cancers (IARC list of 13)Obstructive jaundice and biliary obstructionPerineural invasion (PNI)Peritoneum and peritoneal metastasesResectable, borderline resectable and unresectableRetroperitoneumStenting (biliary, oesophageal, airway)Tumour markerWhipple procedure (pancreaticoduodenectomy)

trials

9
AMPLIFY-7PLow-dose olanzapine for cancer anorexia (Tata Memorial)NAPOLI 3PANOVA-3POLOPonsegromab phase 2 in cancer cachexiaPREOPANC-1 / PREOPANC-2PRODIGE 24 / CCTG PA6RASolute 302

pairings

2
G12D-selective + pan-RAS(ON) inhibitor (zoldonrasib + daraxonrasib)Personalised neoantigen vaccine + PD-1 blockade

roadmaps

2
Early detection roadmap: organ screening → blood tests for many cancersKRAS roadmap: undruggable → G12C → pan-RAS

ideas

61
A billion-dollar prize for the first durable cure of a lethal metastatic cancerA blood test for the pre-metastatic nicheA dietitian in every gastrointestinal and head and neck tumour boardA guaranteed purchase prize for the first drug against a named hard targetA permanent neutral non-profit sponsor for multi-company platform trialsA perpetual platform trial in every major cancer, funded as infrastructureA ring-fenced metastasis programme with metastasis-specific endpointsA standing platform trial for every major cancer, funded as infrastructureA trial of GLP-1 weight-loss drugs with cancer as the primary outcomeAI that spots pancreatic cancer on scans taken a year before diagnosisAnchor a TGF-beta trap in the tumour stroma so it cannot act everywhereAutomatic germline testing for every cancer type where it changes careAutomatic palliative care referral triggered by diagnosis, not by declineBlock the complement signal that recruits tumour-protecting cellsBlood-based pancreatic cancer detection in new-onset diabetesBreak the neutrophil DNA nets that catch tumour cells after surgeryBurden-weighted portfolio targets for every major cancer funderCan MYC be drugged directly, and will patients tolerate it?Catch wasting early with a smart scale and a step counterClear the suppressive neutrophils out of pancreatic tumours firstCombine the new anti-wasting antibody with exercise and proteinCompeting sponsors share one control arm in the same indicationConfirm low-dose olanzapine for appetite and weight in advanced cancer worldwideCovalent chemistry for the RAS mutations that still have no drugCoverage-with-evidence registries for MR-guided and adaptive radiotherapyCure-focused prizes: pay for verified long-term cures, not for drugsCut the nerve supply to tumours with old drugsDe-acidify the tumour so T cells can work in itDedicated cohorts for patients with performance status 2 in first-line trialsEngineered bacteria that live in tumours and manufacture drugs thereEvery routine CT scan checked by AI for early cancer signs, with a tracked follow-up pathwayFAP theranostics as a pan-cancer stromal strategyFAPI PET as the workup for MCED positivesFour weeks of training and nutrition before major cancer surgery, as standardGet the one approved appetite drug licensed beyond a single countryGlucose monitor data as an early pancreatic cancer signalGrow each trial patient's tumour as organoids to decide which platform arm opens nextIn vivo CAR-T against solid-tumour antigensLink bariatric and GLP-1 registries to cancer registries in every country that has bothLosartan to loosen the stroma of pancreatic cancer before chemotherapy: a phase 3Make bespoke mouse cancer models in weeks with in vivo gene editingMake every cold tumour hot: a coordinated programme to reprogramme immune-excluded tumoursMatch therapy to the type of scar-forming cell in the tumourmRNA-delivered MYC decoy proteins instead of MYC inhibitorsNew diabetes after 50 plus weight loss triggers a pancreatic cancer checkOff-the-shelf KRAS vaccines after pancreatic cancer surgeryPartial lottery funding for good proposals in under-funded cancersPersonalised cancer vaccines at commodity cost through fully automated manufacturingPersonalised vaccines given only when the blood test turns positivePublic risk-adjusted outcome reporting for cancer surgery to drive centralisationRapid diagnostic centres for people with vague but worrying symptomsRAS(ON) inhibitors to convert unresectable pancreatic cancer to resectableReprogramme suppressive macrophages instead of trying to delete themSelect cachexia trial patients by the hormone driving their wastingShared concurrent control arms across sponsors' trials in the same settingSoften the tissue that new metastases need in order to growStop watching stable low-risk pancreatic cysts after five yearsTest DPYD, UGT1A1 and TPMT/NUDT15 before the first dose, everywhereTreat cachexia as a disease: GDF-15 blockade plus anabolic and nutrition bundlesTreat cachexia before it startsZebrafish avatars for a drug answer within a week

collections

1
Pancreatic Cancer Action Network (PanCAN)

people

27
Albert C. KoongAndrew J. AguirreAnirban MaitraBert VogelsteinCostas A. LyssiotisDavid A. TuvesonDo-Youn OhDung T. LeEileen M. O'ReillyElizabeth M. JaffeeFrank McCormickGiampaolo TortoraKevan M. ShokatLin ShenPeter J. O'DwyerPeter W. T. PistersPhilip D. GreenbergRaffit HassanRandy PauschRobert H. VonderheideSelwyn M. VickersSusan M. DomchekTanios Bekaii-SaabTheodore S. HongTheodore S. LawrenceTobias JanowitzVolker Heinemann

bottlenecks

11
Cachexia, toxicity and the limits of the patientCold tumours and the immunosuppressive microenvironmentFragmented care and guideline gapsFunding follows fashion, not burdenIncentives reward me-too drugs and marginal gainsInherited risk is mostly unidentifiedMost lethal cancers are found latePain relief and palliative care are unavailable to mostPreclinical models that do not predict peopleThe undruggable driversTumour heterogeneity and clonal evolution

key papers

6
Fifty years of the British Doctors Study: smokers lose ten years of life, quitting gives most of it backIARC verdict: excess body fat causes 13 cancersLe 2017: mismatch-repair deficiency predicts response to PD-1 blockade across twelve tumour types, leading to the first tissue-agnostic drug approvalNAPOLI-3: NALIRIFOX versus gemcitabine plus nab-paclitaxel as first treatment for metastatic pancreatic cancerOstrem and Shokat: the hidden pocket that made KRAS G12C druggableRojas 2023: a personalised mRNA vaccine trained T cells against each patient's pancreatic cancer, and those who responded stayed cancer-free longer