Role of next-generation genomic sequencing in targeted agents repositioning for pancreaticoduodenal cancer patients

Melisi, Davide; Cavaliere, Alessandro; Gobbo, Stefano; Fasoli, Giulia; Allegrini, Valentina; Simionato, Francesca; Gaule, Marina; Casalino, Simona; Pesoni, Camilla; Zecchetto, Camilla; Merz, Valeria; Mambrini, Andrea; Barbi, Emilio; Girelli, R.; Giardino, Alessandro; Frigerio, Isabella; Scalamogna, R.; Avitabile, Arianna; Castellani, Silvia; Milella, Michèle; Butturini, Giovanni

doi:10.1016/j.pan.2021.04.004

Cited by 8 publications

(9 citation statements)

References 31 publications

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“…This novel fusion gene was pathogenetic, and the patient achieved a radiologic partial response maintained for almost 1 year with the RAF inhibitor sorafenib. 7 The reasons for these frequent fusion genes involving KANK4 in PACC deserve further explorations.…”

Section: Discussionmentioning

confidence: 99%

“…In patients affected by PDAC, the most frequent actionable mutations present in approximately 15% of tumor samples belong to the family of genes involved in DNA repair, potentially leading to a sensitivity to poly (ADP-ribose) polymerase-1 inhibitors. 7 In PACC, however, a radically different mutational landscape has been identified if compared with the more frequent PDAC, with recurrent rearrangements involving the actionable genes BRAF and RAF1 in 23% of the cases. ALK rearrangements are extremely rare in PDAC, with only five cases positive of 3,170 cases the largest series studied.…”

Section: Discussionmentioning

confidence: 99%

“…6 Small-molecule inhibitors with activity against RAF demonstrated clinical activity in patients with PACC-positive for RAF1 gene fusions. 7 Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that can be mutated in several tumors, more commonly in 3%-7% of non-small-cell lung cancer (NSCLC), resulting in dysregulation and inappropriate signaling through the ALK kinase domain. Activation of the ALK gene can occur by rearrangements with partner genes, point mutations, or amplification.…”

Section: Introductionmentioning

confidence: 99%

“…6 Small-molecule inhibitors with activity against RAF demonstrated clinical activity in patients with PACC-positive for RAF1 gene fusions. 7…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Exceptional Clinical Response to Alectinib in Pancreatic Acinar Cell Carcinoma With a Novel ALK-KANK4 Gene Fusion

Gaule

Pesoni

Quinzii

et al. 2022

JCO Precision Oncology

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…6 Small-molecule inhibitors with activity against RAF demonstrated clinical activity in patients with PACC-positive for RAF1 gene fusions. 7…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Exceptional Clinical Response to Alectinib in Pancreatic Acinar Cell Carcinoma With a Novel ALK-KANK4 Gene Fusion

Gaule

Pesoni

Quinzii

et al. 2022

JCO Precision Oncology

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“…These results indicated that in advanced pancreaticoduodenal cancer, NGS is a feasible and valuable method for enabling precision oncology. However, this genomic profiling method might be considered only after standard treatments failure, and especially in young patients maintaining a good performance status, in order to detect potentially actionable mutations and offer molecularly targeted therapeutic approaches ( 87 ).…”

Section: Molecular Profiling In Personalizing Therapeutic Strategy In...mentioning

confidence: 99%

Predictive Biomarkers for a Personalized Approach in Resectable Pancreatic Cancer

et al. 2022

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The mainstay treatment for patients with immediate resectable pancreatic cancer remains upfront surgery, which represents the only potentially curative strategy. Nevertheless, the majority of patients surgically resected for pancreatic cancer experiences disease relapse, even when a combination adjuvant therapy is offered. Therefore, aiming at improving disease free survival and overall survival of these patients, there is an increasing interest in evaluating the activity and efficacy of neoadjuvant and perioperative treatments. In this view, it is of utmost importance to find biomarkers able to select patients who may benefit from a preoperative therapy rather than upfront surgical resection. Defined genomic alterations and a dynamic inflammatory microenvironment are the major culprits for disease recurrence and resistance to chemotherapeutic treatments in pancreatic cancer patients. Signal transduction pathways or tumor immune microenvironment could predict early recurrence and response to chemotherapy. In the last decade, distinct molecular subtypes of pancreatic cancer have been described, laying the bases to a tailored therapeutic approach, started firstly in the treatment of advanced disease. Patients with homologous repair deficiency, in particular with mutant germline BRCA genes, represent the first subgroup demonstrating to benefit from specific therapies. A fraction of patients with pancreatic cancer could take advantage of genome sequencing with the aim of identifying possible targetable mutations. These genomic driven strategies could be even more relevant in a potentially curative setting. In this review, we outline putative predictive markers that could help in the next future in tailoring the best therapeutic strategy for pancreatic cancer patients with a potentially curable disease.

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Comparison of genomic profiling of circulating tumor DNA in pancreaticobiliary malignancies in plasma and bile

Ohyama

Hirotsu

Amemiya

et al. 2023

Cancer

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Background: Obtaining sufficient pancreaticobiliary tumor tissue for genomic profiling has limitations. Liquid biopsies using plasma do not provide sufficient sensitivity. Thus, this study aimed to determine the effectiveness of liquid biopsy between bile and plasma for identifying oncogenic and drug-matched mutations.Methods: This study created a panel of 60 significantly mutated genes specific to pancreaticobiliary cancer (PBCA) and used it for genomic analysis of 212 deoxyribonucleic acid (DNA) samples (87 bile supernatant, 87 bile precipitate, and 38 plasma) from 87 patients with PBCA. The quantity of extracted DNA from bile and plasma was compared, as were genomic profiles of 38 pairs of bile and plasma from 38 patients with PBCA. Finally, we investigated 87 bile and 38 plasma for the ability to detect druggable mutations. Results:The amount of DNA was significantly lower in plasma than in bile (p < .001).Oncogenic mutations were identified in 21 of 38 (55%) patients in bile and nine (24%) in plasma samples (p = .005). Bile was significantly more sensitive than plasma in identifying druggable mutations (p = .032). The authors detected 23 drugmatched mutations in combined bile and plasma, including five ERBB2, four ATM, three BRAF, three BRCA2, three NF1, two PIK3CA, one BRCA1, one IDH1, and one PALB2.Conclusions: Liquid biopsy using bile may be useful in searching for therapeutic agents, and using the obtained genomic information may improve the prognoses of patients with PBCA.

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Role of next-generation genomic sequencing in targeted agents repositioning for pancreaticoduodenal cancer patients

Cited by 8 publications

References 31 publications

Exceptional Clinical Response to Alectinib in Pancreatic Acinar Cell Carcinoma With a Novel ALK-KANK4 Gene Fusion

Exceptional Clinical Response to Alectinib in Pancreatic Acinar Cell Carcinoma With a Novel ALK-KANK4 Gene Fusion

Predictive Biomarkers for a Personalized Approach in Resectable Pancreatic Cancer

Comparison of genomic profiling of circulating tumor DNA in pancreaticobiliary malignancies in plasma and bile

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