Signaling Pathways in Cancer: Therapeutic Targets, Combinatorial Treatments, and New Developments

Abstract

Molecular alterations in cancer genes and associated signaling pathways are used to inform new treatments for precision medicine in cancer. Small molecule inhibitors and monoclonal antibodies directed at relevant cancer-related proteins have been instrumental in delivering successful treatments of some blood malignancies (e.g., imatinib with chronic myelogenous leukemia (CML)) and solid tumors (e.g., tamoxifen with ER positive breast cancer and trastuzumab for HER2-positive breast cancer). However, inherent limitations such as drug toxicity, as well as acquisition of de novo or acquired mechanisms of resistance, still cause treatment failure. Here we provide an up-to-date review of the successes and limitations of current targeted therapies for cancer treatment and highlight how recent technological advances have provided a new level of understanding of the molecular complexity underpinning resistance to cancer therapies. We also raise three basic questions concerning cancer drug discovery based on molecular markers and alterations of selected signaling pathways, and further discuss how combination therapies may become the preferable approach over monotherapy for cancer treatments. Finally, we consider novel therapeutic developments that may complement drug delivery and significantly improve clinical response and outcomes of cancer patients.

The Curious Case of the HepG2 Cell Line: 40 Years of Expertise

“…[ 155 ]. Signalome study provides another level for deciphering pathological processes and uses it to inform new treatments for precision medicine in cancer [ 156 ]. However, at the moment many aspects are still unknown, and the current level of information is limited.…”

PI3K/Akt/mTOR Pathway and Its Role in Cancer Therapeutics: Are We Making Headway?

“…Understanding the abnormal expression of cancer pathway genes that play a vital role in cancer genesis and progression will contribute to cancer therapies. Based on current cancer genomic investigations, several critical cancer pathways are abnormally regulated ( 13 ). The PI3K/AKT/mTOR signaling pathway has been described as one of the most commonly disrupted pathways in cancer, making it an attractive candidate for therapeutic intervention.…”

Generation and functional characterization of murine mammary organoids

“…These techniques allow a comprehensive characterization of the molecular properties of newly established mammary epithelial cells with distinct genetic alterations, and cultured in a 3D-setting, and can be used to monitor the status of clinically-relevant molecular markers (e.g., ER, Figure 9 ), over time. The generation and exploitation of 3D mammary organoid cultures can provide an important avenue for the identification of more effective anti-cancer treatments ( Yip and Papa, 2021 ).…”