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Dear Colleagues,

Drug resistance is a complex phenomenon resulting from one or more mechanisms which render cells resistant to anticancer drugs. Molecular hallmarks of cancer and therapeutics against drug resistance mechanisms are the leading targets for cancer treatment. Molecular targeted therapy is gaining attraction due to its specificity to cancer while sparing normal cells. Despite this, drug resistance still representsa major obstacle that limits sustained clinical benefits not only to targeted cancer therapies, but also conventional chemotherapy. Notably, while some cancer patients do not respond to anticancer drugs due to primary resistance, even responders might eventually relapse following acquired resistance.

In this context, we are proposing a new Special Issue encompassing these two major molecular pathways involved in cancer treatment such as the determinations of new cancer related molecular targets, development of drugs that block them and drugs that aims resistance to treatment. We invite innovative research papers and review articles discussing new molecular targets or anticancer drugs. We encourage articles related, but not restricted to Apoptosis Induction, Proliferative Signaling, Migration, Angiogenesis, Metastasis, Immune Checkpoint, Tumor Vaccine Related Targets, Chimeric Antigen Receptor T-Cell or their possible drug resistance mechanisms. Therefore, this special issue is aimed to approach novel molecular targets, their bullets and possible resistance mechanisms that might be targeted to potentiate more durable and effective responses for cancer therapy.

Dr. Bruno Kaufmann Robbs
Dr. Fernando de Carvalho da Silva
Guest Editors

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Related Special Issue

Published Papers (1 paper)

Other

15 pages, 1431 KiB

Open AccessSystematic Review

Clinical Outcomes and Molecular Predictors of Pembrolizumab (Keytruda) as a PD-1 Immune Checkpoint Inhibitor in Advanced and Metastatic Cervical Cancer: A Systematic Review and Meta-Analysis

by Lavinia Balan, Anca Maria Cimpean, Prashant Sunil Nandarge, Bogdan Sorop, Catalin Balan, Madalina Alexandra Balica, Felix Bratosin, Simona Brasoveanu, Madalina Boruga and Laurentiu Pirtea

Biomedicines 2024, 12(5), 1109; https://doi.org/10.3390/biomedicines12051109 - 16 May 2024

Viewed by 430

Abstract

This systematic review evaluates the clinical outcomes and molecular predictors of response to pembrolizumab in patients with advanced and metastatic cervical cancer. We adhered to the PRISMA guidelines for systematic reviews, conducting a database search in PubMed, Scopus, and Embase. The eligibility criteria centered on clinical outcomes, including the overall survival (OS), progression-free survival (PFS), and immune-related biomarkers post-pembrolizumab therapy. We included both prospective and retrospective studies that detailed clinical outcomes and molecular characteristics predictive of therapeutic response. Our search yielded six studies involving 846 patients treated with pembrolizumab from 2017 to 2022. The meta-analysis of these studies showed that pembrolizumab, used as monotherapy or in combination with chemotherapy, extended the OS by a weighted median of 10.35 months and the PFS by 8.50 months. The treatment demonstrated a pooled objective response rate (ORR) of 22.39%, although the I² test result of 67.49% showed a high heterogeneity among the studies. Notably, patients with high PD-L1 expression (CPS ≥ 10) experienced improved outcomes in terms of the PFS and OS. The most common complications were fatigue, diarrhea, and immune-related adverse events. Pembrolizumab significantly enhances clinical outcomes in metastatic cervical cancer, particularly among patients with high PD-L1 expression. The drug maintains a good safety profile, reinforcing its treatment potential for patients with advanced and metastatic cervical cancer. Future studies should explore long-term effects and strategies to integrate pembrolizumab optimally into current treatment regimens, aiming to maximize patient benefits and effectively manage side effects. Full article

(This article belongs to the Special Issue Drug Resistance and Novel Targets for Cancer Therapy—Second Edition)

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