Are All Anti-Angiogenic Drugs the Same in the Treatment of Second-Line Metastatic Colorectal Cancer? Expert Opinion on Clinical Practice

Lai, Eleonora; Cascinu, Stefano; Scartozzi, Mario

doi:10.3389/fonc.2021.637823

Cited by 12 publications

(9 citation statements)

References 124 publications

(156 reference statements)

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“…In addition to inhibiting the VEGF/VEGFR pathway, TKI drugs may also inhibit targets related to immune regulation, such as platelet-derived growth factor receptor (PDGFR), angiopoietin-2 receptor (TIE2), and colony-stimulating factor 1 receptor, and have stronger synergy with immunotherapy. [92][93][94] EGFR EGFR is a member of the epidermal growth factor receptor (HER) family, which includes HER1 (erbB1, EGFR), HER2 (erbB2, NEU), HER3 (erbB3), and HER4 (erbB4). 95,96 Studies have shown that EGFR is overexpressed or abnormally expressed in many solid tumors.…”

Section: Vegf/vegfrmentioning

confidence: 99%

Immune Checkpoint Inhibitor-Based Combination Therapy for Colorectal Cancer: An Overview

Li¹,

Xu²

2023

IJGM

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Colorectal cancer (CRC) is one of the most common diseases in the world. Tumor immunotherapy is an innovative cancer treatment that acts by activating the human body's autoimmune system. Immune checkpoint block has been shown to be effective in DNA deficient mismatch repair/microsatellite instability-high CRC. However, the therapeutic effect for proficient mismatch repair/ microsatellite stability patients still requires further study and optimization. At present, the main CRC strategy is to combine other therapeutic methods, such as chemotherapy, targeted therapy, and radiotherapy. Here, we review the current status and the latest progress of immune checkpoint inhibitors in the treatment of CRC. At the same time, we consider therapeutic opportunities for transforming cold to hot, as well as perspectives on possible future therapies, which may be in great demand for drug-resistant patients.

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Section: Vegf/vegfrmentioning

confidence: 99%

Immune Checkpoint Inhibitor-Based Combination Therapy for Colorectal Cancer: An Overview

Li¹,

Xu²

2023

IJGM

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“…Generally, anti-angiogenic and anti-kinase agents are combinatorically administrated with fluoropyrimidine-based chemotherapy plus OXP and/or IRI ( 189 , 190 ). Among these, the following are clinically approved and used in mCRC treatment regimens: bevacizumab (VEGF inhibitor), aflibercept (blocks activation of VEGF-A, VEGF-B, and PIGF), ramucirumab (anti-VEGFR-2 monoclonal antibody), and regorafenib ( 191 ) with approval and reimburse differently applied in the countries. This last one is a multikinase inhibitor that not only acts on angiogenic protein kinases (VEGFR-1, VEGFR-2, VEGFR-3, TIE-2), but as well on proteins involved in oncogenesis (KIT, RET, RAF-1, BRAF, BRAF V600 ), metastasis (PDGFR, FGFR), and tumor immunity (CSF1R) ( 192 , 193 ).…”

Section: Liquid Biopsy In Colorectal Malignanciesmentioning

confidence: 99%

Liquid Biopsy and Artificial Intelligence as Tools to Detect Signatures of Colorectal Malignancies: A Modern Approach in Patient’s Stratification

et al. 2022

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Colorectal cancer (CRC) is the second most frequently diagnosed type of cancer and a major worldwide public health concern. Despite the global efforts in the development of modern therapeutic strategies, CRC prognosis is strongly correlated with the stage of the disease at diagnosis. Early detection of CRC has a huge impact in decreasing mortality while pre-lesion detection significantly reduces the incidence of the pathology. Even though the management of CRC patients is based on robust diagnostic methods such as serum tumor markers analysis, colonoscopy, histopathological analysis of tumor tissue, and imaging methods (computer tomography or magnetic resonance), these strategies still have many limitations and do not fully satisfy clinical needs due to their lack of sensitivity and/or specificity. Therefore, improvements of the current practice would substantially impact the management of CRC patients. In this view, liquid biopsy is a promising approach that could help clinicians screen for disease, stratify patients to the best treatment, and monitor treatment response and resistance mechanisms in the tumor in a regular and minimally invasive manner. Liquid biopsies allow the detection and analysis of different tumor-derived circulating markers such as cell-free nucleic acids (cfNA), circulating tumor cells (CTCs), and extracellular vesicles (EVs) in the bloodstream. The major advantage of this approach is its ability to trace and monitor the molecular profile of the patient’s tumor and to predict personalized treatment in real-time. On the other hand, the prospective use of artificial intelligence (AI) in medicine holds great promise in oncology, for the diagnosis, treatment, and prognosis prediction of disease. AI has two main branches in the medical field: (i) a virtual branch that includes medical imaging, clinical assisted diagnosis, and treatment, as well as drug research, and (ii) a physical branch that includes surgical robots. This review summarizes findings relevant to liquid biopsy and AI in CRC for better management and stratification of CRC patients.

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“…These factors induce tumors to acquire more angiogenic and invasive potentials, promoting metastasis [ 144 ] . Preclinical studies and clinical trials suggest that inhibition of a specific growth factor can induce the expression of others [ 145 ] . For instance, in a phase II study in which mCRC patients were treated with a combination of 5-FU, leucovorin and irinotecan (FOLFIRI) and bevacizumab, several angiogenic factors, including the placental growth factor and hepatocyte growth factor, were found to increase before disease progression [ 146 ] .…”

Section: Resistance To Targeted Therapymentioning

confidence: 99%

Emerging actionable targets to treat therapy-resistant colorectal cancers

Grassilli¹,

Cerrito²

2022

CDR

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In the last two decades major improvements have been reached in the early diagnosis of colorectal cancer (CRC) and, besides chemotherapy, an ampler choice of therapeutic approaches is now available, including targeted and immunotherapy. Despite that, CRC remains a “big killer” mainly due to the development of resistance to therapies, especially when the disease is diagnosed after it is already metastatic. At the same time, our knowledge of the mechanisms underlying resistance has been rapidly expanding which allows the development of novel therapeutic options in order to overcome it. As far as resistance to chemotherapy is concerned, several contributors have been identified such as: intake/efflux systems upregulation; alterations in the DNA damage response, due to defect in the DNA checkpoint and repair systems; dysregulation of the expression of apoptotic/anti-apoptotic members of the BCL2 family; overexpression of oncogenic kinases; the presence of cancer stem cells; and the composition of the tumoral microenvironment and that of the gut microbiota. Interestingly, several mechanisms are also involved in the resistance to targeted and/or immunotherapy. For example, overexpression and/or hyperactivation and/or amplification of oncogenic kinases can sustain resistance to targeted therapy whereas the composition of the gut microbiota, as well as that of the tumoral niche, and defects in DNA repair systems are crucial for determining the response to immunotherapy. In this review we will make an overview of the main resistance mechanisms identified so far and of the new therapeutic approaches to overcome it.

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Are All Anti-Angiogenic Drugs the Same in the Treatment of Second-Line Metastatic Colorectal Cancer? Expert Opinion on Clinical Practice

Cited by 12 publications

References 124 publications

Immune Checkpoint Inhibitor-Based Combination Therapy for Colorectal Cancer: An Overview

Immune Checkpoint Inhibitor-Based Combination Therapy for Colorectal Cancer: An Overview

Liquid Biopsy and Artificial Intelligence as Tools to Detect Signatures of Colorectal Malignancies: A Modern Approach in Patient’s Stratification

Emerging actionable targets to treat therapy-resistant colorectal cancers

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