Treatment of metastatic castration-resistant prostate cancer: review of current evidence and synthesis of expert opinions on radioligand therapy.

Background: Despite the boom in the development of cancer management in the last decade, most patients with metastatic prostate cancer (PCa) eventually progress to metastatic castration-resistant PCa (mCRPC) and often require multiple lines of treatment. The treatment landscape of mCRPC has evolved rapidly in recent years, introducing various types of systemic therapies, including taxane-based chemotherapy, androgen receptor pathway inhibitors, bone-targeted radionuclides (e.g.

Combinatorial functionomics identifies HDAC6-dependent molecular vulnerability of radioresistant head and neck cancer.

Background: Radiotherapy is the primary treatment modality for most head and neck cancers (HNCs). Despite the addition of chemotherapy to radiotherapy to enhance its tumoricidal effects, almost a third of HNC patients suffer from locoregional relapses. Salvage therapy options for such recurrences are limited and often suboptimal, partly owing to divergent tumor and microenvironmental factors underpinning radioresistance.

Genomic and transcriptomic profiling of radioresistant prostate and head and neck cancers implicate a BAHD1-dependent modification of DNA damage at the heterochromatin.

Radiotherapy is an integral modality in treating human cancers, but radioresistance remains a clinical challenge due to the involvement of multiple intrinsic cellular and extrinsic tumour microenvironment factors that govern radiosensitivity. To study the intrinsic factors that are associated with cancer radioresistance, we established 4 radioresistant prostate (22Rv1 and DU145) and head and neck cancer (FaDu and HK1) models by irradiating their wild-type parentals to 90 Gy, mimicking the fractionated radiotherapy schema that is often using in the clinic, and performed whole exome and transcriptome sequencing of the radioresistant and wild-type models. Comparative genomic analyses detected the enrichment of mismatch repair mutational signatures (SBS6, 14, 15, 20) across all the cell lines and several non-synonymous single nucleotide variants involved in pro-survival pathways.