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Anis A Hamid

Publications and source records attributed to Anis A Hamid.

2 recordsLinked to original sources
PubMed2026

Tumor-Intrinsic Blood and Imaging Correlatives in Advanced Prostate Cancer Treated with Combination Radiopharmaceutical Therapy and Immunotherapy.

The PRINCE trial showed the clinical activity for 177Lu-PSMA-617 in combination with pembrolizumab for metastatic castration-resistant prostate cancer. To refine patient selection and improve response monitoring strategies to this combination, we investigated candidate tumor-intrinsic biomarkers of treatment response and resistance. Methods: We performed circulating tumor DNA (ctDNA), circulating tumor cell (CTC), and PET imaging analyses at baseline, 12 wk on-treatment, and disease progression in participants enrolled in PRINCE (n = 37). We performed targeted sequencing for ctDNA quantification and genomic analysis of more than 70 prostate cancer genes. CTC enumeration was performed on the EpicSciences platform and was combined with selective single-cell whole-genome sequencing. PET imaging included serial PSMA PET as well as 18F-FDG PET imaging at baseline. Results: A low baseline ctDNA fraction and high PSMA avidity in metastatic lesions were linked to superior treatment responses and may have composite biomarker value. Genomic alterations in tumor suppressor genes TP53, RB1, or PTEN were associated with higher 18F-FDG avidity and metabolic tumor volume on 18F-FDG PET imaging and worse prognosis. At 12-wk on-treatment, both ctDNA detection and PSMA PET imaging were strong indicators of response depth and durability. At disease progression, PSMA expression on PET imaging was lower compared with baseline and supported by subclonal remodeling of ctDNA and CTC copy number profiles and by clonal expansions of tumor suppressor gene mutations. Conclusion: We provide the first integrated molecular and imaging insights into determinants of response and resistance to combined radiopharmaceutical therapy and immunotherapy in prostate cancer and propose biomarker strategies to inform future clinical development.

177Lu-PSMA-617↗
PubMed2026

Integrated signatures define mutational processes in prostate cancer.

Prostate cancer follows a long and heterogeneous disease course with incompletely understood aetiology1. Here we dissect the mutational processes shaping the genomes of 959 donors from the Pan Prostate Cancer Group and assess their clinical relevance. By integrating de novo extracted single-base substitution, insertion-deletion and copy-number signatures with six novel complex structural variant signatures, we identify eight integrated mutational footprints (IMFs) that collectively explain the mutational processes in 85% of primary prostate cancer genomes. IMFs were strongly influenced by regional biases in the genome, most prevalently androgen receptor-mediated mutagenesis and replication stress. Four IMFs, present in 37% of primary tumours, were significantly associated with shorter time to metastasis. These included reactive oxygen-species-driven mutagenesis and both canonical and non-canonical homologous recombination deficiency, the latter being enriched in patients of African ancestry. Extending to the metastatic setting, we found that IMFs predicted sensitivity to androgen receptor pathway inhibitors. Taken together, our study delineates the aetiologies and mutational processes that drive the genomic and clinical heterogeneity of prostate cancer, introduces IMFs as a unifying framework, and highlights their potential to improve both risk stratification and biomarker-guided treatment selection.

Journal Article↗