Exploiting LRRC15 as a Novel Therapeutic Target in Cancer

Area of Science:

• Oncology
• Cancer Biology
• Drug Development

Background:

• Tumor stroma plays a key role in cancer progression, promoting oncogenesis, therapy resistance, and metastasis.
• Leucine-rich repeat-containing protein 15 (LRRC15) is implicated in cell-matrix interactions and overexpressed in various mesenchymal tumors and cancer-associated fibroblasts.
• Targeting tumor stroma, particularly LRRC15, is an emerging strategy in cancer therapy.

Purpose of the Study:

• To review the role of LRRC15 in cancer.
• To discuss the potential of LRRC15-targeted therapies, including antibody-drug conjugates (ADCs).
• To identify knowledge gaps and future clinical avenues for LRRC15-positive cancers.

Main Methods:

• Literature review focusing on LRRC15's role in cancer.
• Analysis of preclinical and clinical data for LRRC15-targeted therapies.
• Examination of LRRC15 as a potential predictive biomarker.

Main Results:

• LRRC15 is overexpressed in mesenchymal tumors (sarcoma, glioblastoma, melanoma) and cancer-associated fibroblasts in multiple tumor types.
• Antibody-drug conjugates (ADCs) targeting LRRC15 demonstrate potential for treating LRRC15-positive cancers.
• LRRC15 expression may serve as a predictive biomarker for patient selection.

Conclusions:

• LRRC15 is a viable therapeutic target in oncology, especially for mesenchymal-derived tumors and those with stromal desmoplasia.
• LRRC15-targeted therapies, such as the ABBV-085 ADC, offer a promising approach for personalized cancer treatment.
• Further clinical exploration is needed to optimize therapeutic outcomes for patients with LRRC15-positive cancers.