The most frequently used standard treatment for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer patients consists of a CDK4/6 inhibitor (abemaciclib, ribociclib, or palbociclib) combined with endocrine therapy. Despite CDK4/6 inhibitors being part of routine care in the last few years, new adverse events continue to be reported. Here, we report two cases of palinopsia, a rare neurological visual disturbance that refers to the persistence or recurrence of a visual image after the removal of visual stimuli in patients treated with ribociclib and letrozole. Neuro-ophthalmological assessments and brain MRIs did not find any organic cause. However, palinopsia was related in a time- and dose-dependent manner to the intake of ribociclib. Following a one-level dose reduction of ribociclib, palinopsia was mild and well tolerated. Both patients continued the treatment with ribociclib, with one of them for almost 2 years. Based on the identification of two cases in our hospital in a short period of time, it is tempting to suggest that ribociclib-related palinopsias may not be uncommon. We propose that physicians should be aware of this ribociclib-associated adverse event. Patients presenting this symptom should undergo a routine workup (neuro-ophthalmological assessment and brain MRI) and, if negative, be reassured of its relation with ribociclib as well as the safety of continuing on this drug.
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http://dx.doi.org/10.3389/fonc.2024.1430341 | DOI Listing |
ESMO Open
January 2025
UPMC Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, USA.
Background: Randomized controlled trials have shown inconsistent overall survival (OS) benefit among the three cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) as first-line (1L) treatment of patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC). Several real-world studies compared CDK4/6i effectiveness, with inconsistent findings. This study compared overall survival (OS) of patients with HR+/HER2- mBC receiving 1L palbociclib, ribociclib, or abemaciclib, in combination with an aromatase inhibitor (AI), in US clinical practice.
View Article and Find Full Text PDFJ Med Chem
January 2025
Department of Chemistry, The Hong Kong University of Science and Technology, Hong Kong SAR 999077, China.
CDK4/6 inhibitors are effective in treating HR/HER2 breast cancer but face limitations due to therapeutic resistance and hematological toxicity, particularly from strong CDK6 inhibition. To address these challenges, designing selective inhibitors targeting specific cyclin-dependent kinases (CDK) members could offer clinical advantages and broaden CDK inhibitor indications. However, the highly conserved binding pockets of CDKs complicate selective targeting.
View Article and Find Full Text PDFJ Nanobiotechnology
January 2025
State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University, 169 Changle West Road, 710032, Xi'an, People's Republic of China.
CDK4/6i, the first-line drug for treating ERα-positive breast cancer, significantly improves clinical outcomes. However, CDK4/6i resistance often develops and remains a major hurdle, and the underlying mechanisms remain challenging to fully investigate. Here, we used Genome-wide CRISPR/Cas9 library screening combined with single-cell sequencing to screen for molecules mediating CDK4/6i resistance and identified METTL14 as a determinant of CDK4/6i sensitivity.
View Article and Find Full Text PDFFront Oncol
December 2024
Hospital del Mar, Parc de Salut Mar, Barcelona, Spain.
The most frequently used standard treatment for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer patients consists of a CDK4/6 inhibitor (abemaciclib, ribociclib, or palbociclib) combined with endocrine therapy. Despite CDK4/6 inhibitors being part of routine care in the last few years, new adverse events continue to be reported. Here, we report two cases of palinopsia, a rare neurological visual disturbance that refers to the persistence or recurrence of a visual image after the removal of visual stimuli in patients treated with ribociclib and letrozole.
View Article and Find Full Text PDFNat Commun
January 2025
MultiplexDX, s.r.o., Comenius University Science Park, Bratislava, Slovakia.
Current assays fail to address breast cancer's complex biology and accurately predict treatment response. On a retrospective cohort of 1082 female breast tissues, we develop and validate mFISHseq, which integrates multiplexed RNA fluorescent in situ hybridization with RNA-sequencing, guided by laser capture microdissection. This technique ensures tumor purity, unbiased whole transcriptome profiling, and explicitly quantifies intratumoral heterogeneity.
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