Although one in five colorectal cancers having microsatellite instability and expressing the Werner Helicase (WRN) gene could be treated with drugs that inhibit WRN, the effectiveness of such an approach has been limited by resistance. However, researchers identified the Cys727 mutation as being solely responsible for WRN inhibitor resistance. This potentially opens the door to using WRN inhibitors in the cancer clinic by inactivating this resistance gene.

At the EORTC-NCI-AACR 2024 Molecular Targets and Cancer Therapeutics Symposium Gabriele Picco, PhD, Senior Staff Scientist in the Translational Cancer Genomics Team at the Wellcome Sanger Institute’s Genome Campus, reported findings about WRN resistance mechanisms that may clear the path to introducing WRN inhibitors to the cancer clinic to fight microsatellite unstable cancers. 

A tumor-agnostic classifier and screening tool was announced at ESMO Congress 2024 in Barcelona. It was created to make it easier and quicker to develop new drugs that have specific molecular targets, and thus have potential anti-cancer efficacy irrespective of tumor type or location.

The ESMO Tumour-Agnostic Classifier and Screener was the result of work by a multidisciplinary team of international experts led by the ESMO Precision Medicine Working Group. At the conference, Benedikt Westphalen, MD, a medical oncologist and molecular biologist who is Head of the Precision Oncology Program at the University of Munich in Germany, talked about the details with Oncology Times correspondent Peter Goodwin.

Findings from a study of patients receiving targeted therapy for their BRAFV600 mutation-positive advanced melanoma, suggest that switching early to immune checkpoint inhibition appeared to bring better rates of overall survival than saving immunotherapy for use as salvage treatment later on.

The ESMO 2024 Annual Congress heard from the randomized Phase II ImmunoCobiVem trial that a switch to immunotherapy after only 3 months treatment with drugs targeted to the mutation gave equivalent or better survival than continuing with targeted therapy.

A clinically meaningful benefit in overall survival was found in the second interim analysis of the randomized, double-blind, Phase III KEYNOTE-A18 study of immunotherapy together with concurrent chemoradiotherapy among 1,060 patients who had newly diagnosed, previously untreated high-risk locally advanced cervical cancer.

A multinational team of researchers, led from Italy, reported findings at the ESMO Congress 2024. There was a statistically significant increase in 36-month overall survival in patients treated with pembrolizumab, in addition to chemoradiotherapy, in comparison to those in the control group who received standard chemoradiation alone.

The prospect of markedly raising chemotherapy response rates and extending patient survival has been held out by scientists reporting a new AI-powered digital tool to optimize cancer management for individual patients.

The tool creates a “digital twin” for each patient that makes it possible to predict response to specific treatment regimens and confidently predict outcomes, according to findings from a study reported by scientists at the EORTC-NCI-AACR 2024 Molecular Targets and Cancer Therapeutics Symposium.

The prospect of a minimally toxic, chemotherapy-free cure for hepatoblastoma is held out by findings from a mouse model using the small-molecule drug WNTinib that inhibits the Wnt signaling pathway involved with cancer growth.

Lead author Ugnė Balaševičiūtė, a pre-doctoral researcher in Translational Research of the Hepatic Oncology Group led by Josep M. Llovet, Professor at the Institut D'Investigacions Biomediques August Pi i Sunyer (IDIBAPS) in Barcelona, Spain, reported that the CTNNB1 (catenin beta-1 protein) gene targeted by WNTinib was expressed in 90 percent of all hepatoblastomas. Hopes were high that a safer alternative to chemotherapy in humans was on the way.

A chemotherapy-free combination of two anti-human epidermal growth factor receptor 2 (anti-HER2) agents brought clinically meaningful responses to patients with bile duct cancers testing positive for HER2 or with mutated HER2 in research from Japan reported at the EORTC-NCI-AACR 2024 Molecular Targets and Cancer Therapeutics Symposium held in Barcelona, Spain.

In the SGNTUC-019 Phase II basket study of 217 patients, who had a variety of previously treated solid tumors with HER2 overexpressed, amplified, or mutated, a combination of tucatinib with trastuzumab brought significant clinical responses among those with biliary tract tumors in addition to those with breast cancer.