bims-ovdlit 2022-08-14 papers

Issue of 2022–08–14
four papers selected by
Lara Paracchini, Humanitas Research

Arch Immunol Ther Exp (Warsz). 2022 Aug 09. 70(1): 19

Natalia Siminiak, Rafał Czepczyński, Mikołaj Piotr Zaborowski, Dariusz Iżycki.

Despite advances in surgery and chemotherapy, ovarian cancer remains one of the most lethal malignancies. Hence, the implementation of novel treatment approaches is required to improve the outcomes of the disease. Immunotherapy has been proven to be effective in many tumors and has already been incorporated into clinical practice. In this review, we describe key strategies in immunotherapy of ovarian cancer and summarize data from clinical studies assessing immunological prospects which could improve ovarian cancer treatment approaches in the future. The most notable current strategies include checkpoint blockade agents, the use of vaccines, adoptive cell transfer, as well as various combinations of these methods. While several of these options are promising, large controlled randomized studies are still needed to implement new immunotherapeutic options into clinical practice.

Keywords: Adoptive transfer; Immunotherapy; Ovarian cancer; Vaccine

DOI: https://doi.org/10.1007/s00005-022-00655-8

Nature. 2022 08;608(7922): 360-367

Spatially resolved clonal copy number alterations in benign and malignant tissue.

Defining the transition from benign to malignant tissue is fundamental to improving early diagnosis of cancer1. Here we use a systematic approach to study spatial genome integrity in situ and describe previously unidentified clonal relationships. We used spatially resolved transcriptomics2 to infer spatial copy number variations in >120,000 regions across multiple organs, in benign and malignant tissues. We demonstrate that genome-wide copy number variation reveals distinct clonal patterns within tumours and in nearby benign tissue using an organ-wide approach focused on the prostate. Our results suggest a model for how genomic instability arises in histologically benign tissue that may represent early events in cancer evolution. We highlight the power of capturing the molecular and spatial continuums in a tissue context and challenge the rationale for treatment paradigms, including focal therapy.

DOI: https://doi.org/10.1038/s41586-022-05023-2

Science. 2022 Apr 22. pii: science.abl9283. [Epub ahead of print]376(6591):

Substitution mutational signatures in whole-genome-sequenced cancers in the UK population.

Genomics England Research Consortium

Whole-genome sequencing (WGS) permits comprehensive cancer genome analyses, revealing mutational signatures, imprints of DNA damage and repair processes that have arisen in each patient's cancer. We performed mutational signature analyses on 12,222 WGS tumor-normal matched pairs, from patients recruited via the UK National Health Service. We contrasted our results to two independent cancer WGS datasets, the International Cancer Genome Consortium (ICGC) and Hartwig Foundation, involving 18,640 WGS cancers in total. Our analyses add 40 single and 18 double substitution signatures to the current mutational signature tally. Critically, we show for each organ, that cancers have a limited number of 'common' signatures and a long tail of 'rare' signatures. We provide a practical solution for utilizing this concept of common versus rare signatures in future analyses.

DOI: https://doi.org/10.1126/science.abl9283

Gynecol Oncol. 2022 Aug 03. pii: S0090-8258(22)00513-3. [Epub ahead of print]

What happens after menopause? (WHAM): A prospective controlled study of symptom profiles up to 12 months after pre-menopausal risk-reducing salpingo-oophorectomy.

Katrina M Moss, Gita D Mishra, Efrosinia O Krejany, Martha Hickey.

OBJECTIVE: Understanding how symptoms cluster after premenopausal risk-reducing salpingo-oophorectomy (RRSO) can inform patient expectations but information is lacking. We aimed to identify symptom profiles after RRSO, changes over time, and the effect of hormone therapy (HT).
METHOD: Participants were premenopausal women from a longitudinal controlled study (What Happens After Menopause? (WHAM)). Menopausal symptoms were prospectively measured in three groups: pre-menopausal comparisons who retained their ovaries (n = 99), RRSO HT users (n = 57) and RRSO non-HT users (n = 38). Symptoms (hot flashes, night sweats, low desire, vaginal dryness, poor sleep, anxiety/depression) were measured at baseline (pre-surgery) and at 3, 6 and 12 months using standardised questionnaires. Latent transition analysis was used to identify symptom profiles post-RRSO, and the probability of changing profiles over time.
RESULTS: Three symptom profiles were identified: Most Symptoms (81-87% non-HT; 36-41% HT; 7-9% comparisons), Few Symptoms (7-13% non-HT; 36-42% HT; 77-80% comparisons), and Sexual Symptoms (0-10% non-HT; 17-27% HT; 14-15% comparisons). Most of the non-HT group reported Most Symptoms at 3 months with only a 2% chance of improvement by 12 months. The HT group were split between profiles at 3 months with a 5-13% chance of improvement by 6 months (14% chance of worsening), and a 12-32% chance of improvement by 12 months (4-25% chance of worsening).
CONCLUSIONS: Symptoms cluster into distinct profiles after premenopausal RRSO. Most non-HT users are highly symptomatic with little chance of improvement by 12 months. In contrast, two-thirds of HT users have fewer symptoms and a much higher chance of improvement. These findings can inform patient decision-making and expectations.

Keywords: Latent transition analysis; Menopausal symptoms; Risk-reducing salpingo-oophorectomy; Surgical menopause

DOI: https://doi.org/10.1016/j.ygyno.2022.07.029