The role of PIGF blockade in the treatment of colorectal cancer: overcoming the pitfalls

Macarulla, Teresa; Montagut, Clara; Sánchez-Martín, Francisco Javier; Granja, Mónica; Verdaguer, Helena; Sastre, Javier; Tabernero, Josep

doi:10.1080/14712598.2020.1677603

Cited by 19 publications

(21 citation statements)

References 73 publications

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“…High expression of the PGF gene in gastric cancer was associated with an increased risk of lymph node metastasis and serosal invasion, and shorter survival [46]. PGF was reported to be associated with an angiogenesis pathway different from VEGF, and PGF blockade combined with the 5-FU + Folinic acid + Irinotecan (FOLFIRI) regimen improved the survival of patients with metastatic colorectal cancer who had resistance to chemotherapy [47]. PGF signaling was also reported to contribute to the anti-tumor effect of metformin in breast cancer [48].…”

Section: Discussionmentioning

confidence: 99%

A Novel 4-gene Score to Predict Survival, Distant Metastasis and Response to Neoadjuvant Therapy in Breast Cancer

Oshi

Katsuta

Yan

et al. 2020

Cancers

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We generated a 4-gene score with genes upregulated in LM2-4, a metastatic variant of MDA-MB-231 (DOK 4, HCCS, PGF, and SHCBP1) that was strongly associated with disease-free survival (DFS) in TCGA cohort (hazard ratio [HR]>1.2, p < 0.02). The 4-gene score correlated with overall survival of TCGA (HR = 1.44, p < 0.001), which was validated with DFS and disease-specific survival of METABRIC cohort. The 4-gene score was able to predict worse survival or clinically aggressive tumors, such as high Nottingham pathological grade and advanced cancer staging. High score was associated with worse survival in the hormonal receptor (HR)-positive/Her2-negative subtype. High score enriched cell proliferation-related gene sets in GSEA. The score was high in primary tumors that originated, in and metastasized to, brain and lung, and it predicted worse progression-free survival for metastatic tumors. Good tumor response to neoadjuvant chemotherapy or hormonal therapy was accompanied by score reduction. High scores were also predictive of response to neoadjuvant chemotherapy for HR-positive/Her2-negative subtype. High score tumors had increased expression of T cell exhaustion marker genes, suggesting that the score may also be a biomarker for immunotherapy response. Our novel 4-gene score with both prognostic and predictive values may, therefore, be clinically useful particularly in HR-positive breast cancer.

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Section: Discussionmentioning

confidence: 99%

A Novel 4-gene Score to Predict Survival, Distant Metastasis and Response to Neoadjuvant Therapy in Breast Cancer

Oshi

Katsuta

Yan

et al. 2020

Cancers

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“…Anti-angiogenic agents also act by normalizing the blood vessel texture, which is convoluted and dysfunctional in cancer, thus increasing blood flow and suggesting that the administration of an anti-angiogenic drug plus chemotherapy increases the delivery of the chemotherapeutic agent to the cancer tissue ( 60 ). Preclinical studies showed the tumor capability to develop compensatory mechanisms leading to restoration of high vessel density and consequently cancer growth; this phenomenon appears related to hypoxia-triggered upregulation of alternative pro-angiogenic factors ( 19 ). The biomarker landscape in mCRC is evolving ( 61 ), but unfortunately to date, no biomarkers to define which patients will respond to anti-angiogenic treatment and who will develop resistance have been validated yet, although several have been investigated (tissue-based or circulating).…”

Section: Resistance Mechanismsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Tumor angiogenesis leads to the formation of new blood vessels through a very complex and coordinated process ( 16 – 19 ). Physiologic angiogenesis is a well-controlled event, regulated via the balance of pro- and antiangiogenic factors ( 19 ). Among these, the vascular endothelial growth factor (VEGF) signaling represents a key pathway and it comprises a family of five secreted proteins [VEGF-A, VEGF-B, VEGF-C, VEGF-D, and placental growth factor (PlGF)] and three receptor tyrosine kinases (RTK): VEGF receptor (VEGFR)-1, VEGFR-2, and VEGFR-3 ( 19 , 20 ).…”

Section: Introductionmentioning

confidence: 99%

“…Physiologic angiogenesis is a well-controlled event, regulated via the balance of pro- and antiangiogenic factors ( 19 ). Among these, the vascular endothelial growth factor (VEGF) signaling represents a key pathway and it comprises a family of five secreted proteins [VEGF-A, VEGF-B, VEGF-C, VEGF-D, and placental growth factor (PlGF)] and three receptor tyrosine kinases (RTK): VEGF receptor (VEGFR)-1, VEGFR-2, and VEGFR-3 ( 19 , 20 ). VEGFR-1 [also named Fms-like tyrosine kinase-1 (FLT1)] and VEGFR-3 [also named Fms-related tyrosine kinase 4 (FLT4)] have been shown to be involved in tumor progression and metastasis in CRC, and VEGFR-2 (also named fetal liver kinase FLK1/KDR) has been implicated in endothelial cell survival, proliferation and migration ( 21 , 22 ).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

2021

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Targeting tumor-driven angiogenesis is an effective strategy in the management of metastatic colorectal cancer (mCRC); however, the choice of second-line therapy is complicated by the availability of several drugs, the occurrence of resistance and the lack of validated prognostic and predictive biomarkers. This review examines the use of angiogenesis-targeted therapies for the second-line management of mCRC patients. Mechanisms of resistance and anti-placental growth factor agents are discussed, and the role of aflibercept, a recombinant fusion protein consisting of portions of human vascular endothelial growth factor receptor (VEGFR)-1 and VEGFR-2, is highlighted. The novel mechanism of action of aflibercept makes it a useful second-line agent in mCRC patients progressing after oxaliplatin-based chemotherapy, as well as in those with resistance after bevacizumab.

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Patient profiles as an aim to optimize selection in the second line setting: the role of aflibercept

et al. 2021

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Colorectal cancer is the second leading cause of cancer-related death worldwide. For metastatic colorectal cancer (mCRC) patients, it is recommended, as first-line treatment, chemotherapy (CT) based on doublet cytotoxic combinations of fluorouracil, leucovorin, and irinotecan (FOLFIRI) and fluorouracil, leucovorin, and oxaliplatin (FOLFOX). In addition to CT, biological (targeted agents) are indicated in the first-line treatment, unless contraindicated. In this context, most of mCRC patients are likely to progress and to change from first line to second line treatment when they develop resistance to first-line treatment options. It is in this second line setting where Aflibercept offers an alternative and effective therapeutic option, thought its specific mechanism of action for different patient’s profile: RAS mutant, RAS wild-type (wt), BRAF mutant, potentially resectable and elderly patients. In this paper, a panel of experienced oncologists specialized in the management of mCRC experts have reviewed and selected scientific evidence focused on Aflibercept as an alternative treatment.

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The role of PIGF blockade in the treatment of colorectal cancer: overcoming the pitfalls

Cited by 19 publications

References 73 publications

A Novel 4-gene Score to Predict Survival, Distant Metastasis and Response to Neoadjuvant Therapy in Breast Cancer

A Novel 4-gene Score to Predict Survival, Distant Metastasis and Response to Neoadjuvant Therapy in Breast Cancer

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

Patient profiles as an aim to optimize selection in the second line setting: the role of aflibercept

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