4.5 Review

Novel systemic treatment approaches for metastatic pancreatic cancer

Journal

EXPERT OPINION ON INVESTIGATIONAL DRUGS
Volume 31, Issue 3, Pages 249-262

Publisher

TAYLOR & FRANCIS LTD
DOI: 10.1080/13543784.2022.2037552

Keywords

Pancreatic cancer; metastatic; immunotherapy; targeted therapy; cellular therapy; novel drugs

Funding

  1. international doctoral program 'i-Target: Immunotargeting of cancer' - Elite Network of Bavaria
  2. Melanoma Research Alliance [409510]
  3. Marie-Sklodowska-Curie Program Training Network for Optimizing Adoptive T Cell Therapy of Cancer - H2020 Program of the European Union [955575]
  4. Else Kroner-Fresenius-Stiftung
  5. German Cancer Aid
  6. Ernst-Jung-Stiftung by LMU Munichs Institutional Strategy LMUexcellent within German Excellence Initiative
  7. Bundesministerium fur Bildung und Forschung
  8. Bavarian Ministry of Economical Affairs (M4-award)
  9. European Research Council Starting Grant [756017]
  10. Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [SFB-TRR 338/1 2021 -452881907]
  11. Fritz-BenderFoundation
  12. Jose-Carreras Foundation
  13. Hector Foundation

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With a 5-year overall survival rate of 10%, more effective therapies are needed for metastatic PDAC. Emerging drugs in clinical development, including cellular therapies, are being investigated to overcome the challenges of the immunosuppressive tumor microenvironment, poor vascularization, and dense tumor stroma typical for PDAC. Exciting clinical trials are ongoing, with a focus on targeted treatments and personalized therapy plans for PDAC patients.
Introduction Pancreatic ductal adenocarcinoma (PDAC) has a 5-year overall survival rate of 10%, emphasizing the need for more effective therapies, especially in metastatic disease. The immunosuppressive tumor microenvironment, poor vascularization, and dense tumor stroma typical for PDAC are hurdles that need to be overcome by novel drugs. Investigations are moving toward more targeted treatments including immunotherapy and cell-based approaches. Areas covered This article reviews emerging drugs in clinical development for metastatic PDAC, focusing on cellular therapies and novel treatments targeting metabolism, tumor stroma, oncogenic pathways and immunosuppression. With immunotherapy and CAR T-cell therapy on the rise in hematological malignancies, the transfer to solid tumors remains intriguing. Multiple exciting clinical trials investigating innovative therapeutic strategies for PDAC are currently ongoing and reviewed herein. ClinicalTrials.gov, conference abstracts and PubMed were searched in August 2021 and assessed for information on ongoing and published clinical studies. Expert opinion With many challenges to overcome, the optimal therapy for patients with metastatic PDAC is likely to consist of a combination of different agents. We are slowly moving from entity-dependent approaches to ones more focused on molecular and pathological features. Increasingly personalized treatment plans tailored to each patient may be the future of PDAC therapy.

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