A Comparative Study of Methyl-BEAMing and Droplet Digital PCR for Gene Promoter Hypermethylation Detection.

is responsible for the direct repair of O6-methylguanine lesions induced by alkylating agents, including temozolomide. promoter hypermethylation is a well-established biomarker for temozolomide response in glioblastoma patients, also correlated with therapeutic response in colorectal cancer. The ARETHUSA clinical trial aims to stratify colorectal cancer patients based on their mismatch repair status.

Curative immune checkpoint inhibitors therapy in patients with mismatch repair-deficient locally advanced rectal cancer: a real-world observational study.

Background: Sustained clinical complete remissions were reported in all of 23 mismatch repair deficient/microsatellite instable (dMMR/MSI) locally advanced rectal cancer (LARC) patients treated with dostarlimab alone in a recent phase II study. These results led to off-label use of dostarlimab or other immune checkpoint inhibitors (ICIs) in dMMR/MSI-LARC even before regulatory approval. The present study [STAR(t)-IT-REDUCE] describes the outcome of dMMR/MSI-LARC patients treated with ICI in Italy.

Ongoing Clinical Trials and Future Research Scenarios of Circulating Tumor DNA for the Treatment of Metastatic Colorectal Cancer.

Liquid biopsy using circulating tumor DNA (ctDNA) has emerged as a minimally invasive, timely approach to provide molecular diagnosis and monitor tumor evolution in patients with cancer. Since the molecular landscape of metastatic colorectal cancer (mCRC) is substantially heterogeneous and dynamic over space and time, ctDNA holds significant advantages as a biomarker for this disease. Numerous studies have demonstrated that ctDNA broadly recapitulates the molecular profile of the primary tumor and metastases, and have mainly focused on the genotyping of RAS and BRAF, that is propaedeutic for anti-EGFR treatment selection.

Clinicopathological characterisation of alterations in gastrointestinal cancers.

Background: Methylthioadenosine phosphorylase (MTAP) is an essential metabolic enzyme in the purine and methionine salvage pathway. In cancer, gene copy number loss ( loss) confers a selective dependency on the related protein arginine methyltransferase 5. The impact of alterations in gastrointestinal (GI) cancers remains unknown although hypothetically druggable.

Esophageal Cancer with Early Onset in a Patient with Cri du Chat Syndrome.

Background: In Cri du Chat (CdC), cancer as comorbidity is extremely rare. In databases from Denmark, Spain, Australia, New Zealand, and Japan, no cancer was reported; in Italy and Germany, four cancers were identified out of 321 CdCs.

Methods: In a 29-year-old CdC patient, clinical investigations following hematemesis led to the diagnosis of esophageal adenocarcinoma (EAC).

Circulating Tumor DNA to Drive Treatment in Metastatic Colorectal Cancer.

In the evolving molecular treatment landscape of metastatic colorectal cancer (mCRC), the identification of druggable alterations is pivotal to achieve the best therapeutic opportunity for each patient. Because the number of actionable targets is expanding, there is the need to timely detect their presence or emergence to guide the choice of different available treatment options. Liquid biopsy, through the analysis of circulating tumor DNA (ctDNA), has proven safe and effective as a complementary method to address cancer evolution while overcoming the limitations of tissue biopsy.

Young-onset colorectal cancer: treatment-related nausea, vomiting and diarrhoea.

Objectives: Early-onset colorectal cancer (EO-CRC) incidence is increasing, raising a clinical challenge. Clinicians tend to treat EO-CRC patients with more intensive regimens despite the lack of survival benefits, based on an age-related bias. Limited evidence is available regarding treatment-related toxicities in this peculiar subset of patients.

Corrigendum: Case report: mutation is associated with primary resistance to anti-EGFR monoclonal antibodies in metastatic colorectal cancer.

[This corrects the article DOI: 10.3389/fonc.2022.

Case Report: mutation is associated with primary resistance to anti-EGFR monoclonal antibodies in metastatic colorectal cancer.

Background: We aim to identify the prevalence and the role of the mutation in predicting resistance to anti-EGFR agents in metastatic colorectal cancer (mCRC) patients.

Methods: We retrospectively reviewed tumor-based next generation sequencing (NGS) results from mCRC patients screened for enrollment in the GO40872/STARTRK-2 clinical trial between July 2019 and March 2021. Then, in patients harboring microsatellite stable (MSS) and wild-type mutant mCRC, we reviewed outcome to treatment with anti-EGFR monoclonal antibodies.

Efficacy of Retreatment with Oxaliplatin-Based Regimens in Metastatic Colorectal Cancer Patients: The RETROX-CRC Retrospective Study.

Background: oxaliplatin with fluoropyrimidine is a "mainstay" regarding the upfront treatment of metastatic colorectal cancer (mCRC). In contrast, the efficacy and safety of oxaliplatin-based regimens in late-care settings have been poorly reported.

Methods: we identified a real-world mCRC patient cohort who were re-treated with oxaliplatin, and in which clinicopathological features were retrospectively analyzed to identify efficacy-predictive determinants (RETROX-CRC study).

Chemotherapy toxicity and activity in patients with pancreatic ductal adenocarcinoma and germline BRCA1-2 pathogenic variants (gBRCA1-2pv): a multicenter survey.

Background: Germline BRCA1-2 pathogenic variants (gBRCA1-2pv)-related pancreatic ductal adenocarcinoma (PDAC) showed increased sensitivity to DNA cross-linking agents. This study aimed at exploring safety profile, dose intensity, and activity of different chemotherapy regimens in this setting.

Patients And Methods: gBRCA1-2pv PDAC patients of any age and clinical tumor stage who completed a first course of chemotherapy were eligible.

Liquid Biopsy for Prognosis and Treatment in Metastatic Colorectal Cancer: Circulating Tumor Cells vs Circulating Tumor DNA.

Liquid biopsy recently gained widespread attention as a noninvasive alternative/complementary technique to tissue biopsy in patients with cancer. As technological advances have improved both feasibility and turnaround time, liquid biopsy has expanded tumor molecular analysis with acknowledgement of both spatial and temporal heterogeneity, overcoming many limitations of traditional tissue biopsy. Because of its diagnostic, prognostic, and predictive value, liquid biopsy has been extensively studied also in metastatic colorectal cancer.

Chemotherapy-induced myasthenic crisis in thymoma treated with primary chemotherapy with curative intent on mechanical ventilation: a case report and review of the literature.

Background: Thymoma is an uncommon cancer often associated with myasthenia gravis, an autoimmune disorder of the neuromuscular junction characterized by muscular fatigability. In patients with advanced nonmetastatic thymoma, primary chemotherapy may be required to induce tumor shrinkage and to achieve radical resection. Cancer chemotherapy has been anecdotally reported as a trigger factor for worsening of myasthenia gravis in thymic epithelial cancers.

The Evolutionary Landscape of Treatment for Mutant Metastatic Colorectal Cancer.

The mutation is found in 8-10% of metastatic colorectal cancer (mCRC) patients and it is recognized as a poor prognostic factor with a median overall survival inferior to 20 months. At present, besides immune checkpoint inhibitors (CPIs) for those tumors with concomitant MSI-H status, recommended treatment options include cytotoxic chemotherapy + anti-VEGF in the first line setting, and a combination of EGFR and a BRAF inhibitor (cetuximab plus encorafenib) in second line. However, even with the latter targeted approach, acquired resistance limits the possibility of more than an incremental benefit and survival is still dismal.

Oxaliplatin retreatment in metastatic colorectal cancer: Systematic review and future research opportunities.

Background: Oxaliplatin represents a main component of cytotoxic treatment regimens in colorectal cancer (CRC). Given its efficacy, oxaliplatin is frequently re-administered in the context of the continuum of care in metastatic CRC (mCRC). However, efficacy and tolerability of this therapeutic strategy has not been comprehensively assessed.

Pertuzumab and trastuzumab emtansine in patients with HER2-amplified metastatic colorectal cancer: the phase II HERACLES-B trial.

Background: HER2 is a therapeutic target for metastatic colorectal cancer (mCRC), as demonstrated in the pivotal HERACLES-A (HER2 Amplification for Colo-rectaL cancer Enhanced Stratification) trial with trastuzumab and lapatinib. The aim of HERACLES-B trial is to assess the efficacy of the combination of pertuzumab and trastuzumab-emtansine (T-DM1) in this setting.

Methods: HERACLES-B was a single-arm, phase II trial, in patients with histologically confirmed wild-type and HER2+ mCRC refractory to standard treatments.

Long-term Clinical Outcome of Trastuzumab and Lapatinib for HER2-positive Metastatic Colorectal Cancer.

Background: ERBB2 amplification occurs in 5% of RAS wild-type metastatic colorectal cancer (mCRC) and it has been shown to be a target for treatment with 2 HER2-directed combinations of trastuzumab and lapatinib or trastuzumab and pertuzumab. We present long-term clinical results of trastuzumab and lapatinib (HERACLES-A trial) at 6.7 years (82 months) follow-up and focus on central nervous system (CNS) recurrences.

The Quest for Improving Treatment of Cancer of Unknown Primary (CUP) Through Molecularly-Driven Treatments: A Systematic Review.

Carcinomas of unknown primary (CUP) account for 3-5% of all malignancy and, despite a reduction in incidence, the overall survival has not improved over the last decade. Chemotherapy regimens have not provided encouraging results. New diagnostic technologies, such as next generation sequencing (NGS), could represent a chance to identify potentially targetable genomic alterations in order to personalize treatment of CUP and provide insights into tumor biology.

Tropomyosin receptor kinase (TRK) biology and the role of NTRK gene fusions in cancer.

The tropomyosin receptor kinase (TRK) family of receptor tyrosine kinases are encoded by NTRK genes and have a role in the development and normal functioning of the nervous system. Since the discovery of an oncogenic NTRK gene fusion in colorectal cancer in 1986, over 80 different fusion partner genes have been identified in a wide array of adult and paediatric tumours, providing actionable targets for targeted therapy. This review describes the normal function and physiology of TRK receptors and the biology behind NTRK gene fusions and how they act as oncogenic drivers in cancer.

Liquid biopsy for rectal cancer: A systematic review.

Background: The management of locally advanced rectal cancer (RC) is an evolving clinical field where the multidisciplinary approach can reach its best, and liquid biopsy for obtaining tumor-derived component such as circulating tumor DNA (ctDNA) might provide complementary informations.

Methods: A systematic review of studies available in literature of liquid biopsy in non-metastatic RC has been performed according to PRISMA criteria to assess the role of ctDNA as a diagnostic, predictive and prognostic biomarker in this setting.

Results: Twenty-five publications have been retrieved, of which 8 full-text articles, 7 abstracts and 10 clinical trials.

High Circulating Methylated DNA Is a Negative Predictive and Prognostic Marker in Metastatic Colorectal Cancer Patients Treated With Regorafenib.

Regorafenib improves progression free survival (PFS) in a subset of metastatic colorectal cancer (mCRC) patients, although no biomarkers of efficacy are available. Circulating methylated DNA (cmDNA) assessed by a five-gene panel was previously associated with outcome in chemotherapy treated mCRC patients. We hypothesized that cmDNA could be used to identify cases most likely to benefit from regorafenib (i.

Retreatment with anti-EGFR monoclonal antibodies in metastatic colorectal cancer: Systematic review of different strategies.

Background: Despite advances in precision oncology and immunotherapy of tumors, little progress has been made in metastatic colorectal cancer (mCRC) in recent years. Therefore, making the most of available therapies is a necessity. Several studies, based on the pulsatile behavior of RAS clones under EGFR blockade, investigated whether readministration of EGFR-targeted agents is effective beyond second line.

Ramucirumab as Second-Line Therapy in Metastatic Gastric Cancer: Real-World Data from the RAMoss Study.

Background: Ramucirumab-alone or combined with paclitaxel-represents one of the main options for patients failing first-line treatment for advanced gastric cancer.

Objective: The RAMoss study aimed to evaluate the safety and efficacy profile of ramucirumab in the "real-life setting".

Patients And Methods: Patients from 25 Italian hospitals started therapy consisting of ramucirumab 8 mg/kg i.