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Predictive Immune Modeling of Solid Tumors
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Extrapulmonary poorly differentiated NECs, including molecular and immune aspects.

Mairéad G McNamara1,2, Jean-Yves Scoazec3,4, Thomas Walter5

  • 1Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK.

Endocrine-Related Cancer
|May 2, 2020
PubMed
Summary

Extrapulmonary poorly differentiated neuroendocrine carcinomas (EP-PD-NECs) have poor outcomes. This review summarizes current treatments, molecular insights, and immune data for EP-PD-NECs, highlighting areas for future research and novel drug discovery.

Keywords:
extra-pulmonaryimmune landscapemolecular profileneuroendocrine carcinomapoorly differentiatedtreatment

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Area of Science:

  • Oncology
  • Genetics
  • Immunology

Background:

  • Extrapulmonary poorly differentiated neuroendocrine carcinomas (EP-PD-NECs) are aggressive tumors with limited treatment options.
  • Most patients present with advanced disease, necessitating systemic therapies.
  • Current treatment strategies are often extrapolated from lung neuroendocrine carcinomas.

Purpose of the Study:

  • To review the current treatment landscape for EP-PD-NECs.
  • To explore the known molecular drivers and genetic alterations in EP-PD-NECs.
  • To summarize the emerging data on the immune microenvironment and targeted immunotherapies.

Main Methods:

  • Literature review of existing studies on EP-PD-NECs.
  • Analysis of molecular data from relevant tumor types and identified EP-PD-NEC mutations.
  • Examination of ongoing clinical trials for immunotherapy in EP-PD-NECs.

Main Results:

  • Platinum/etoposide regimens are standard first-line therapy for advanced EP-PD-NECs, with no established second-line treatment.
  • Genetic alterations in TP53, KRAS, PIK3CA/PTEN, and BRAF have been identified, though EP-PD-NEC genetics are not fully understood.
  • Limited data exists on the immune microenvironment, with ongoing trials investigating immune-targeted agents yielding conflicting results.

Conclusions:

  • EP-PD-NECs represent an under-researched malignancy with a poor prognosis.
  • Further research into molecular pathways and immune interactions is crucial for developing novel therapeutic strategies.
  • Biomarkers like circulating tumor cells and cell-free DNA may aid in treatment response prediction.