bims-necame Biomed News
on Metabolism in small cell neuroendocrine cancers
Issue of 2025–06–15
two papers selected by
Grigor Varuzhanyan, UCLA



  1. Front Immunol. 2025 ;16 1560241
      Platinum-based first-line chemotherapy for small lung cancers has been a mainstream therapy for the past several decades. However, its efficacy has been suboptimal, and the research is now focused on improving the treatment and prognosis of competitive nutrition and multidrug combination techniques. Small cell lung cancer (SCLC) is not only affected by smoking, age, sex and other external factors, but also the tumor micro-environment and the nutritional status of patients themselves are of great significance for the prevention and treatment of SCLC, a malignant tumor. According to past research, malnutrition is related to the intolerance to immunotherapy, decline in quality of life, psychological disturbances, and low survival rates and prognosis. Numerous studies have shown that a low Prognostic Nutritional Index (PNI) serves as an independent prognostic factor linked to reduced overall survival across various cancer types. Additionally, PNI has been associated with disease-free survival and progression-free survival in certain cancers, such as lung cancer (LC). Recent research has indicated that the PNI can serve as an independent predictor of both long-term outcomes and short-term complications in SCLC patients. However, a systematic consensus on this matter has yet to be established. This paper focuses on the role and influence of PNI in the immunotherapy of SCLC, and proposes the possibility of dietary therapy for SCLC patients under the guidance of PNI. Finally, the authors pointed out that PNI will become a new strategy for comprehensive immunotherapy of SCLC.
    Keywords:  diet; immunotherapy; nutrition; prognostic nutritional index; small lung cancer
    DOI:  https://doi.org/10.3389/fimmu.2025.1560241
  2. bioRxiv. 2025 Jun 01. pii: 2025.05.28.656673. [Epub ahead of print]
      Cells regularly adapt their metabolism in response to changes in their microenvironment or biosynthetic needs. Prostate cancer cells leverage this metabolic plasticity to evade therapies targeting the androgen receptor (AR) signaling pathway. For example, nucleotide metabolism plays a critical role in treatment-resistant prostate cancer by supporting DNA replication, DNA damage response and cell fate decisions. Identifying novel regulators of nucleotide metabolism in treatment-resistant cancer that are dispensable for the health of normal cells may lead to new therapeutic approaches less toxic than commonly used chemotherapies targeting nucleotide metabolism. We identify the metabolic enzyme Oxoglutarate Dehydrogenase-Like (OGDHL), named for its structural similarity to the tricarboxylic acid (TCA) cycle enzyme Oxoglutarate Dehydrogenase (OGDH), as a regulator of nucleotide metabolism, tumor growth, and treatment-induced plasticity in prostate cancer. While OGDHL is a tumor-suppressor in various cancers, we find that its loss impairs prostate cancer cell proliferation and tumor formation while having minimal impact on TCA cycle activity. Loss of OGDHL profoundly decreases nucleotide metabolite pools, induces the DNA damage response marker Ɣ2AX, and alters androgen receptor inhibition-induced plasticity, including suppressing the neuroendocrine markers DLL3 and HES6. Finally, OGDHL is highly expressed in neuroendocrine prostate cancer (NEPC). These findings support an unexpected role of OGDHL in prostate cancer, where it functions to sustain nucleotide pools for proliferation, DNA repair, and AR inhibition-induced plasticity.
    DOI:  https://doi.org/10.1101/2025.05.28.656673