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<p>Penile carcinoma (PeCa) is a rare malignancy occurring in men. Treatment typically involves penectomy, radiation, or cisplatin-based chemotherapy. A paclitaxel, ifosfamide, and cisplatin-based regimen achieves response rates around 65%. However, non-responders face a 5-year survival rate of only 8%, and due to its rarity, it is mediocrely characterized. Thus, an in-depth delineation of PeCa is crucial to identify novel therapeutic targets. Newly established primary human PeCa cell lines and corresponding xenografts tumors were examined using mass spectrometry and phospho-kinase arrays to analyze the (phospho-)proteome and secretome. Proteomic analyses identified heat shock proteins (HSP27/60/70), factors involved in posttranslational modifications (e.g. acetylation), and the VEGF signaling pathway as putative therapeutic targets. Secreted factors were associated with the HIF-1 and Hippo signaling cascades. Compared to standard chemotherapy (e.g. cisplatin, 5-FU, ifosfamide, irinotecan), treatment with romidepsin, quisinostat (HDAC inhibitors (i)), palbociclib (CDK4/6i), or 17-AAG and PU-H71 (HSP90i) reduced cell viability, induced apoptosis, and led to G2 / M cell cycle arrest in most PeCa cells. This research underscores the therapeutic potential of using HDAC, CDK4/6, and HSP90 inhibitors for PeCa management and reveals additional promising targets and biomarkers for future strategies.</p>

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Targeting histone deacetylation, cell cycle regulators and heat shock proteins as novel therapeutic strategies for penile cancers

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月31日

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  • Lara Marson,
  • Margaretha A. Skowron,
  • Pailin Pongratanakul,
  • Mara Kotthoff,
  • Gereon Poschmann,
  • Hanibal Bohnenberger,
  • Alexa Stephan,
  • Meike M. Watolla,
  • Elvira Mukinovic,
  • Kai Stühler,
  • Thomas Kurz,
  • Hiresh Ayoubian,
  • Johannes Linxweiler,
  • Kerstin Junker,
  • Daniel Nettersheim

摘要

Penile carcinoma (PeCa) is a rare malignancy occurring in men. Treatment typically involves penectomy, radiation, or cisplatin-based chemotherapy. A paclitaxel, ifosfamide, and cisplatin-based regimen achieves response rates around 65%. However, non-responders face a 5-year survival rate of only 8%, and due to its rarity, it is mediocrely characterized. Thus, an in-depth delineation of PeCa is crucial to identify novel therapeutic targets. Newly established primary human PeCa cell lines and corresponding xenografts tumors were examined using mass spectrometry and phospho-kinase arrays to analyze the (phospho-)proteome and secretome. Proteomic analyses identified heat shock proteins (HSP27/60/70), factors involved in posttranslational modifications (e.g. acetylation), and the VEGF signaling pathway as putative therapeutic targets. Secreted factors were associated with the HIF-1 and Hippo signaling cascades. Compared to standard chemotherapy (e.g. cisplatin, 5-FU, ifosfamide, irinotecan), treatment with romidepsin, quisinostat (HDAC inhibitors (i)), palbociclib (CDK4/6i), or 17-AAG and PU-H71 (HSP90i) reduced cell viability, induced apoptosis, and led to G2 / M cell cycle arrest in most PeCa cells. This research underscores the therapeutic potential of using HDAC, CDK4/6, and HSP90 inhibitors for PeCa management and reveals additional promising targets and biomarkers for future strategies.