Avelumab Plus Talazoparib in Patients With BRCA1/2- or ATM-Altered Advanced Solid Tumors: Results From JAVELIN BRCA/ATM, an Open-Label, Multicenter, Phase 2b, Tumor-Agnostic Trial.
Schram Alison M et al. JAMA oncology 2022 11
Is the combination of avelumab and talazoparib effective in patients with pathogenic BRCA1/2 or ATM alterations, regardless of tumor type?
In this phase 2b nonrandomized controlled trial with 200 patients, neither the BRCA1/2 nor ATM cohort met the prespecified target of an objective response rate of 40% across cancer types. Durable clinical activity was observed in patients with BRCA1/2-associated tumor types (eg, ovarian, breast, prostate, and pancreatic cancers) vs those with non–BRCA-associated cancer types; a notable exception were patients with BRCA1/2-altered uterine leiomyosarcoma, who had prolonged responses to treatment.
Spatial genomics maps the structure, nature and evolution of cancer clones.
Lomakin Artem et al. Nature 2022 11
Genome sequencing of cancers often reveals mosaics of different subclones present in the same tumour. We developed a workflow that generates detailed quantitative maps of genetic subclone composition across whole-tumour sections. These provide the basis for studying clonal growth patterns, and the histological characteristics, microanatomy and microenvironmental composition of each clone. The approach rests on whole-genome sequencing, followed by highly multiplexed base-specific in situ sequencing, single-cell resolved transcriptomics and dedicated algorithms to link these layers.
Cancer drugs are closing in on some of the deadliest mutations
H ledford, Nature, October 25, 2022
The protein KRAS, mutated in many cancers, was deemed ‘undruggable’. Now scientists are hoping to save lives with a batch of new compounds that target it.
The KRAS protein sits at the centre of a spiderweb of crucial cellular pathways. It has a role in governing cell proliferation, cell death and many things in between. The KRAS protein cycles between two conformations, switching from an ‘off’ state to an ‘on’ state when it binds to the signalling molecule GTP. Mutations associated with cancer make the protein more likely to linger in its ‘on’ state,and can be found in nearly every type of tumour.
Cancer research needs better databases- Progress on one of the world’s biggest killers will stall without big registries linking scattered records.
T. S. Karin Eisinger-Mathason, Nature, October 25, 2022
The ideal cancer registry would aggregate information from millions of consenting participants; include populations of different ancestry and socio-economic status; collect information going forwards from the time of cancer diagnosis — including imaging, tissue samples and genetic data; and capture participants’ histories by automatically linking to their complete medical records. With these detailed profiles, we could trace cancer diagnoses, health effects and risk of death back to potential risk factors.