bims-tumhet 2023-08-06 papers

Issue of 2023–08–06
five papers selected by
Sergio Marchini, Humanitas Research

Nat Rev Drug Discov. 2023 Jul 31.

APOBEC3A drives resistance.

M Teresa Villanueva.

Keywords: Cancer; Drug discovery; Molecular biology

DOI: https://doi.org/10.1038/d41573-023-00122-9

Nat Cancer. 2023 Jul 31.

Understanding the mechanisms and translational implications of the microbiome for cancer therapy innovation.

Jessica Queen, Fyza Shaikh, Cynthia L Sears.

The intersection of the microbiota and cancer and the mechanisms that define these interactions are a fascinating, rapidly evolving area of cancer biology and therapeutics. Here we present recent insights into the mechanisms by which specific bacteria or their communities contribute to carcinogenesis and discuss the bidirectional interplay between microbiota and host gene or epigenome signaling. We conclude with comments on manipulation of the microbiota for the therapeutic benefit of patients with cancer.

DOI: https://doi.org/10.1038/s43018-023-00602-2

JAMA Netw Open. 2023 08 01. 6(8): e2326834

Time-Dependent Changes in Risk of Progression During Use of Bevacizumab for Ovarian Cancer.

Shiro Takamatsu, Hidekatsu Nakai, Ken Yamaguchi, Junzo Hamanishi, Masaki Mandai, Noriomi Matsumura.

Importance: Although bevacizumab has been used in the treatment of ovarian cancer, its optimal use is unknown.
Objective: To investigate time-dependent changes in the outcomes of bevacizumab therapy.
Design, Setting, and Participants: This cohort study was conducted using published data from 7 previous randomized phase 3 clinical trials with bevacizumab (ICON7, GOG-0218, BOOST, GOG-0213, OCEANS, AURERIA, and MITO16B) from January 10 to January 31, 2023. From 2 ancillary analyses of the ICON7 trial with individual patient data and tumor gene expression profiles, an ICON7-A cohort was generated comprising 745 cases. From other studies, published Kaplan-Meier curves were graphically analyzed.
Exposures: Bevacizumab treatment vs placebo or no treatment.
Main Outcomes and Measures: Restricted mean survival time and relative risk of progression at a given time point between bevacizumab treatment and control groups.
Results: In the ICON7-A cohort (n = 745), restricted mean survival analysis showed that bevacizumab treatment (n = 384) had significantly better progression-free survival (PFS) than the control (n = 361) before bevacizumab discontinuation (restricted mean survival time ratio, 1.08; 95% CI, 1.05-1.11; P < .001), but had significantly worse PFS after bevacizumab discontinuation (0.79; 95% CI, 0.69-0.90; P < .001), showing rebound. In a post hoc analysis, the rebound was similarly observed both in homologous recombination deficiency (HRD) (before, 1.05; 95% CI, 1.02-1.09; P < .001; after, 0.79; 95% CI, 0.63-0.98; P = .04) and non-HRD tumors (before, 1.08; 95% CI, 1.03-1.15; P < .001; after, 0.71; 95% CI, 0.56-0.90; P < .001) of the serous subtype, but not in the nonserous subtype (before, 1.11; 95% CI, 1.05-1.18; P < .001; after, 0.94; 95% CI, 0.78-1.15; P = .57). In Kaplan-Meier curve image-based analysis, the trend of rebound effect was consistently observed in the overall ICON7 and GOG-0218 cohorts and their subgroups stratified by prognostic factors, homologous recombination-associated mutations, and chemotherapy sensitivity. In contrast, no such trend was observed in the studies GOG-0213, OCEANS, AURERIA, and MITO16B, in which patients who experienced relapse received bevacizumab until progression.
Conclusions and Relevance: In ovarian cancer, bevacizumab may reduce progression for approximately 1 year after initiation, but discontinuation may increase subsequent progression in the serous subtype regardless of HRD status. The results suggest that in the first-line treatment, bevacizumab may be more beneficial in patients with a shorter prognosis who are less likely to experience the rebound outcome.

DOI: https://doi.org/10.1001/jamanetworkopen.2023.26834

Clin Cancer Res. 2023 Aug 02. pii: CCR-23-0917. [Epub ahead of print]

The New NCI Precision Medicine Trials.

Basket, umbrella, and platform trial designs (master protocols) have emerged over the last decade to study precision medicine approaches in oncology. First generation trials like NCI-MATCH have proven the principle that studying targeted therapies on a large scale is feasible both from the laboratory and clinical perspectives. However, single agent targeted therapies have shown limited ability to control metastatic disease, despite careful matching of drug to target. As such, newer approaches employing combinations of targeted therapy, or targeted therapy with standard therapies, need to be considered. The NCI has recently embarked on three 2nd generation precision medicine trials to address this need: ComboMATCH, iMATCH, and myeloMATCH. The design of these trials and necessary infrastructure are discussed in the following perspective.

DOI: https://doi.org/10.1158/1078-0432.CCR-23-0917

Crit Rev Clin Lab Sci. 2023 Jul 30. 1-22

Pre-analytical conditions and implementation of quality control steps in liquid biopsy analysis.

Aliki Ntzifa, Evi Lianidou.

Over the last decade, great advancements have been made in the field of liquid biopsy through extensive research and the development of new technologies that facilitate the use of liquid biopsy for cancer patients. This is shown by the numerous liquid biopsy tests that gained clearance by the US Food and Drug Administration (FDA) in recent years. Liquid biopsy has significantly altered cancer treatment by providing clinicians with powerful and immediate information about therapeutic decisions. However, the clinical integration of liquid biopsy is still challenging and there are many critical factors to consider prior to its implementation into routine clinical practice. Lack of standardization due to technical challenges and the definition of the clinical utility of specific assays further complicates the establishment of Standard Operating Procedures (SOPs) in liquid biopsy. Harmonization of laboratories to established guidelines is of major importance to overcome inter-lab variabilities observed. Quality control assessment in diagnostic laboratories that offer liquid biopsy testing will ensure that clinicians can base their therapeutic decisions on robust results. The regular participation of laboratories in external quality assessment schemes for liquid biopsy testing aims to promptly pinpoint deficiencies and efficiently educate laboratories to improve their quality of services. Accreditation of liquid biopsy diagnostic laboratories based on the ISO15189 standard in Europe or by CLIA/CAP accreditation procedures in the US is the best way to achieve the adaptation of liquid biopsy into the clinical setting by assuring reliable results for the clinicians and their cancer patients. Nowadays, various organizations from academia, industry, and regulatory agencies collaborate to set a framework that will include all procedures from the pre-analytical phase and the analytical process to the final interpretation of results. In this review, we underline several challenges in the analysis of circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) concerning standardization of protocols, quality control assessment, harmonization of laboratories, and compliance to specific guidelines that need to be thoroughly considered before liquid biopsy enters the clinic.

Keywords: CTCs; EQA; Liquid biopsy; accreditation; circulating tumor DNA; circulating tumor cells; ctDNA; pre-analytical; quality control

DOI: https://doi.org/10.1080/10408363.2023.2230290