Research

11 pages, 999 KiB

Open AccessArticle

AXL and MET Tyrosine Kinase Receptors Co-Expression as a Potential Therapeutic Target in Malignant Pleural Mesothelioma

by Federica Zito Marino, Carminia Maria Della Corte, Vincenza Ciaramella, Stefania Erra, Andrea Ronchi, Alfonso Fiorelli, Giovanni Vicidomini, Mario Santini, Giosuè Scognamiglio, Floriana Morgillo, Fortunato Ciardiello, Renato Franco and Marina Accardo

J. Pers. Med. 2022, 12(12), 1993; https://doi.org/10.3390/jpm12121993 - 02 Dec 2022

Cited by 2 | Viewed by 1603

Abstract

Malignant pleural mesothelioma (MPM) is a highly lethal malignancy that unfortunately cannot benefit from molecularly targeted therapies. Although previous results showed the pivotal role of various receptor tyrosine kinases (RTKs) in MPM tumorigenesis, the treatment with a single inhibitor targeting one specific RTK [...] Read more.

Malignant pleural mesothelioma (MPM) is a highly lethal malignancy that unfortunately cannot benefit from molecularly targeted therapies. Although previous results showed the pivotal role of various receptor tyrosine kinases (RTKs) in MPM tumorigenesis, the treatment with a single inhibitor targeting one specific RTK has been shown to be ineffective in MPM patients. The main aim of the present study was to investigate the potential role of AXL and MET receptors in MPM and the possible efficacy of treatment with AXL and MET multitarget inhibitors. Immunohistochemical and FISH analyses were performed in a wide series of formalin-fixed paraffin-embedded MPM samples to detect the expression of two receptors and the potential gene amplification. In vitro studies were performed to evaluate putative correlations between the target’s expression and the cell sensitivity to AXL-MET multitarget inhibitors. In our series, 10.4% of cases showed a co-expression of AXL and MET, regardless of their ligand expression, and the gene amplification. Furthermore, our in vitro results suggest that the concomitant pharmacological inhibition of AXL and MET may affect the proliferative and aggressiveness of MPM cells. In conclusion, the subset of MPM patients with AXL-MET co-activation could benefit from treatment with specific multitarget inhibitors. Full article

(This article belongs to the Special Issue The Present and Future of Personalized Medicine in Oncology)

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12 pages, 1122 KiB

Open AccessArticle

Determinants of Treatment Benefit and Post-Treatment Survival for Patients with Hepatocellular Carcinoma Enrolled in Second-Line Trials after the Failure of Sorafenib Treatment

by Nicola Personeni, Tiziana Pressiani, Valentina Zanuso, Andrea Casadei-Gardini, Antonio D’Alessio, Martina Valgiusti, Vincenzo Dadduzio, Francesca Bergamo, Caterina Soldà, Mario Domenico Rizzato, Laura Giordano, Armando Santoro and Lorenza Rimassa

J. Pers. Med. 2022, 12(10), 1726; https://doi.org/10.3390/jpm12101726 - 17 Oct 2022

Viewed by 1458

Abstract

Second-line treatments are standard care for advanced hepatocellular carcinoma (HCC) patients with preserved liver function who are intolerant of or progress on first-line therapy. However, determinants of treatment benefit and post-treatment survival (PTS) remain unknown. HCC patients previously treated with sorafenib and enrolled [...] Read more.

Second-line treatments are standard care for advanced hepatocellular carcinoma (HCC) patients with preserved liver function who are intolerant of or progress on first-line therapy. However, determinants of treatment benefit and post-treatment survival (PTS) remain unknown. HCC patients previously treated with sorafenib and enrolled in second-line clinical trials were pooled according to the investigational treatment received and the subsequent regulatory approval: approved targeted agents and immune checkpoint inhibitors (AT) or other agents (OT) not subsequently approved. Univariate and multivariate analyses using Cox proportional hazards models established relationships among treatments received, clinical variables, and overall survival (OS) or PTS. For 174 patients (80 AT; 94 OT) analyzed, baseline factors for longer OS in multivariate analysis were second-line AT, absence of both portal vein thrombosis and extrahepatic spread (EHS). Treatment with AT (versus OT) was associated with significantly longer OS among patients with EHS (p_interaction = 0.005) and patients with low neutrophil-to-lymphocyte ratio (NLR; p_interaction = 0.032). Median PTS was 4.0 months (95% CI 2.8–5.3). At second-line treatment discontinuation, alpha-fetoprotein (AFP) levels <400 ng/dl, albumin-bilirubin (ALBI) grade 1, and enrolment onto subsequent trials independently predicted longer PTS. Treatment with AT, PVT, and EHS were prognostic factors for OS, while AFP, ALBI grade and enrolment onto a third-line trial were prognostic for PTS. Presence of EHS and low NLR were predictors of greater OS benefit from AT. Full article

(This article belongs to the Special Issue The Present and Future of Personalized Medicine in Oncology)

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12 pages, 1685 KiB

Open AccessArticle

TRANS-TACE: Prognostic Role of the Transient Hypertransaminasemia after Conventional Chemoembolization for Hepatocellular Carcinoma

by Alessandro Granito, Antonio Facciorusso, Rodolfo Sacco, Laura Bartalena, Cristina Mosconi, Ugo Vittorio Cea, Alberta Cappelli, Matteo Antonino, Francesco Modestino, Nicolò Brandi, Francesco Tovoli, Fabio Piscaglia, Rita Golfieri and Matteo Renzulli

J. Pers. Med. 2021, 11(10), 1041; https://doi.org/10.3390/jpm11101041 - 17 Oct 2021

Cited by 53 | Viewed by 2605

Abstract

The aim of the present study was to correlate laboratory data and postprocedural parameters after conventional transarterial chemoembolization (cTACE) for hepatocellular carcinoma (HCC) with the radiological response. The study consisted of a retrospective analysis of prospectively collected data from 70 consecutive patients who [...] Read more.

The aim of the present study was to correlate laboratory data and postprocedural parameters after conventional transarterial chemoembolization (cTACE) for hepatocellular carcinoma (HCC) with the radiological response. The study consisted of a retrospective analysis of prospectively collected data from 70 consecutive patients who underwent cTACE. Laboratory parameters were assessed daily after cTACE and compared to pretreatment values. Post-treatment radiological response was assessed using mRECIST at one month from cTACE, and factors associated with treatment response (complete and objective response) were assessed by logistic regression analysis. The optimal cutoff points in predicting the complete response of target lesions were a 52% ALT and a 46% AST increase after cTACE compared to the pre-treatment values. Using multivariate analyses, >46% AST and >52% ALT increases with respect to the pre-treatment value were significantly correlated with the objective response (p = 0.03 and p = 0.04, respectively) and the complete response (p = 0.02 and p = 0.02, respectively). No patients experienced liver function deterioration after cTACE, and no specific treatment was required. This study showed that post-treatment transient transaminase elevation was predictive of objective response to superselective cTACE in clinical practice, representing a simple tool to guide treatment strategy of HCC patients in a tailored approach. Full article

(This article belongs to the Special Issue The Present and Future of Personalized Medicine in Oncology)

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16 pages, 2088 KiB

Open AccessArticle

HPV Status and Individual Characteristics of Human Papillomavirus Infection as Predictors for Clinical Outcome of Locally Advanced Cervical Cancer

by Liana Mkrtchian, Irina Zamulaeva, Liudmila Krikunova, Valentina Kiseleva, Olga Matchuk, Liubov Liubina, Gunel Kulieva, Sergey Ivanov and Andrey Kaprin

J. Pers. Med. 2021, 11(6), 479; https://doi.org/10.3390/jpm11060479 - 27 May 2021

Cited by 3 | Viewed by 2201

Abstract

This study is aimed at searching for an informative predictor of the clinical outcome of cervical cancer (CC) patients. The study included 135 patients with locally advanced cervical cancer (FIGO stage II–III) associated with human papillomavirus (HPV) 16/18 types or negative status of [...] Read more.

This study is aimed at searching for an informative predictor of the clinical outcome of cervical cancer (CC) patients. The study included 135 patients with locally advanced cervical cancer (FIGO stage II–III) associated with human papillomavirus (HPV) 16/18 types or negative status of HPV infection. Using logistic regression, we analyzed the influence of the treatment method, clinical and morphological characteristics, and the molecular genetic parameters of HPV on the disease free survival (DFS) of patients treated with radiotherapy or chemoradiotherapy. Multivariate analysis revealed three factors that have prognostic significance for DFS, i.e., HPV-related biomarker (HPV-negativity or HPV DNA integration into the cell genome) (OR = 9.67, p = 1.2 × 10⁻⁴), stage of the disease (OR = 4.69, p = 0.001) and age (OR = 0.61, p = 0.025). The predictive model has a high statistical significance (p = 5.0 × 10⁻⁸; Nagelkirk’s R² = 0.336), as well as sensitivity (Se = 0.74) and specificity (Sp = 0.75). Thus, simultaneous accounting for the clinical and molecular genetic predictors (stage of the disease, patient age and HPV-related biomarker) makes it possible to effectively differentiate patients with prognostically favorable and unfavorable outcome of the disease. Full article

(This article belongs to the Special Issue The Present and Future of Personalized Medicine in Oncology)

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Review

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12 pages, 761 KiB

Open AccessReview

Clinical and Novel Biomarkers in Penile Carcinoma: A Prospective Review

by Leonel Pekarek, Miguel A. Ortega, Oscar Fraile-Martinez, Cielo García-Montero, Carlos Casanova, Miguel A. Saez, Natalio García-Honduvilla, Melchor Alvarez-Mon, Julia Buján, Victor Diez-Nicolas, Javier F. Burgos and Victoria Gomez Dos Santos

J. Pers. Med. 2022, 12(9), 1364; https://doi.org/10.3390/jpm12091364 - 24 Aug 2022

Cited by 2 | Viewed by 2671

Abstract

Penile carcinoma is a rare urological neoplasia in men compared to other more common tumors, such as prostate, kidney, or bladder tumors. However, this neoplasm continues to affect a large number of patients worldwide, with developing countries presenting the highest incidence and mortality [...] Read more.

Penile carcinoma is a rare urological neoplasia in men compared to other more common tumors, such as prostate, kidney, or bladder tumors. However, this neoplasm continues to affect a large number of patients worldwide, with developing countries presenting the highest incidence and mortality rates. Important risk factors such as the human papilloma virus, a factor affecting a large number of patients, have been described; however, few studies have evaluated screening programs in populations at risk for this disease, which severely affects the quality of life of older men. The management of these patients is usually complex, requiring surgical interventions that are not without risk and that have a great impact on the functionality of the male reproductive system. In addition, in cases of disseminated disease or with significant locoregional involvement, patients are evaluated by multidisciplinary oncological committees that can adjust the application of aggressive neoadjuvant or adjuvant chemotherapy on numerous occasions without clear improvement in survival. Chemotherapy regimens are usually aggressive, and unlike in other urological neoplasms, few advances have been made in the use of immunotherapy in these patients. The study of serological and histological biomarkers may help to better understand the underlying pathophysiology of these tumors and select patients who have a higher risk of metastatic progression. Similarly, the analysis of molecular markers will improve the availability of targeted therapies for the management of patients with disseminated disease that would benefit prognosis. Therefore, the purpose of this article is to summarize the main advances that have occurred in the development of serological and histological markers and their therapeutic implications in patients diagnosed with penile carcinoma, explaining the limitations that have been observed and analyzing future perspectives in the management of this disease. Full article

(This article belongs to the Special Issue The Present and Future of Personalized Medicine in Oncology)

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16 pages, 440 KiB

Open AccessEditor’s ChoiceReview

Immunotherapy for Squamous Esophageal Cancer: A Review

by Angelica Petrillo and Elizabeth C. Smyth

J. Pers. Med. 2022, 12(6), 862; https://doi.org/10.3390/jpm12060862 - 25 May 2022

Cited by 10 | Viewed by 3907

Abstract

Esophageal squamous cell carcinoma (ESCC) is a rare gastrointestinal tumour with high mortality. A multimodality treatment based on chemoradiotherapy followed by surgery is the standard of care in the case of non-metastatic disease; chemotherapy has historically been the gold standard in the metastatic [...] Read more.

Esophageal squamous cell carcinoma (ESCC) is a rare gastrointestinal tumour with high mortality. A multimodality treatment based on chemoradiotherapy followed by surgery is the standard of care in the case of non-metastatic disease; chemotherapy has historically been the gold standard in the metastatic setting. However, the rate of relapse after curative treatment is high and the prognosis of ESCC is poor. In this context, immunotherapy is a novel and intriguing chance to improve survival. Therefore, in this narrative review, we depict the current scenario in the field of immunotherapy for ESCC according to the stage of disease and alongside the discussion of promising biomarkers and future perspectives. The Checkmate-577 trial showed that nivolumab is the best option as adjuvant treatment in patients with non-metastatic ESCC and residual disease after a multimodality approach. In the metastatic setting, nivolumab, pembrolizumab, camrelizumab, sintilimab and toripalimab improved survival outcomes as a first-line treatment in addition to chemotherapy. In the second-line, nivolumab, pembrolizumab, camrelizumab and tislelizumab showed positive results, with differences according to the subgroups, agents and study population included in the trials. Then, the finding of valid molecular biomarkers is crucial in selecting patients for immunotherapy. Full article

(This article belongs to the Special Issue The Present and Future of Personalized Medicine in Oncology)

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14 pages, 1988 KiB

Open AccessReview

Multi-Omic Approaches in Colorectal Cancer beyond Genomic Data

by Emilia Sardo, Stefania Napolitano, Carminia Maria Della Corte, Davide Ciardiello, Antonio Raucci, Gianluca Arrichiello, Teresa Troiani, Fortunato Ciardiello, Erika Martinelli and Giulia Martini

J. Pers. Med. 2022, 12(2), 128; https://doi.org/10.3390/jpm12020128 - 18 Jan 2022

Cited by 6 | Viewed by 3280

Abstract

Colorectal cancer (CRC) is one of the most frequent tumours and one of the major causes of morbidity and mortality globally. Its incidence has increased in recent years and could be linked to unhealthy dietary habits combined with environmental and hereditary factors, which [...] Read more.

Colorectal cancer (CRC) is one of the most frequent tumours and one of the major causes of morbidity and mortality globally. Its incidence has increased in recent years and could be linked to unhealthy dietary habits combined with environmental and hereditary factors, which can lead to genetic and epigenetic changes and induce tumour development. The model of CRC progression has always been based on a genomic, parametric, static and complex approach involving oncogenes and tumour suppressor genes. Recent advances in omics sciences have sought a paradigm shift to a multiparametric, immunological-stromal, and dynamic approach for a better understanding of carcinogenesis and tumour heterogeneity. In the present paper, we review the most important preclinical and clinical data and present recent discoveries in the field of transcriptomics, proteomics, metagenomics and radiomics in CRC disease. Full article

(This article belongs to the Special Issue The Present and Future of Personalized Medicine in Oncology)

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13 pages, 277 KiB

Open AccessReview

Current Omics Trends in Personalised Head and Neck Cancer Chemoradiotherapy

by Loredana G. Marcu and David C. Marcu

J. Pers. Med. 2021, 11(11), 1094; https://doi.org/10.3390/jpm11111094 - 26 Oct 2021

Cited by 8 | Viewed by 2176

Abstract

Chemoradiotherapy remains the most common management of locally advanced head and neck cancer. While both treatment components have greatly developed over the years, the quality of life and long-term survival of patients undergoing treatment for head and neck malignancies are still poor. Research [...] Read more.

Chemoradiotherapy remains the most common management of locally advanced head and neck cancer. While both treatment components have greatly developed over the years, the quality of life and long-term survival of patients undergoing treatment for head and neck malignancies are still poor. Research in head and neck oncology is equally focused on the improvement of tumour response to treatment and on the limitation of normal tissue toxicity. In this regard, personalised therapy through a multi-omics approach targeting patient management from diagnosis to treatment shows promising results. The aim of this paper is to discuss the latest results regarding the personalised approach to chemoradiotherapy of head and neck cancer by gathering the findings of the newest omics, involving radiotherapy (dosiomics), chemotherapy (pharmacomics), and medical imaging for treatment monitoring (radiomics). The incorporation of these omics into head and neck cancer management offers multiple viewpoints to treatment that represent the foundation of personalised therapy. Full article

(This article belongs to the Special Issue The Present and Future of Personalized Medicine in Oncology)

8 pages, 256 KiB

Open AccessReview

Precision Neurosurgery: A Path Forward

by Vianney Gilard, Stéphane Derrey, Stéphane Marret, Soumeya Bekri and Abdellah Tebani

J. Pers. Med. 2021, 11(10), 1019; https://doi.org/10.3390/jpm11101019 - 12 Oct 2021

Cited by 3 | Viewed by 2471

Abstract

Since the inception of their profession, neurosurgeons have defined themselves as physicians with a surgical practice. Throughout time, neurosurgery has always taken advantage of technological advances to provide better and safer care for patients. In the ongoing precision medicine surge that drives patient-centric [...] Read more.

Since the inception of their profession, neurosurgeons have defined themselves as physicians with a surgical practice. Throughout time, neurosurgery has always taken advantage of technological advances to provide better and safer care for patients. In the ongoing precision medicine surge that drives patient-centric healthcare, neurosurgery strives to effectively embrace the era of data-driven medicine. Neuro-oncology best illustrates this convergence between surgery and precision medicine with the advent of molecular profiling, imaging and data analytics. This convenient convergence paves the way for new preventive, diagnostic, prognostic and targeted therapeutic perspectives. The prominent advances in healthcare and big data forcefully challenge the medical community to deeply rethink current and future medical practice. This work provides a historical perspective on neurosurgery. It also discusses the impact of the conceptual shift of precision medicine on neurosurgery through the lens of neuro-oncology. Full article

(This article belongs to the Special Issue The Present and Future of Personalized Medicine in Oncology)

Other

Jump to: Research, Review

7 pages, 250 KiB

Open AccessOpinion

Will Organoids Fill the Gap towards Functional Precision Medicine?

by Federica Papaccio, Manuel Cabeza-Segura, Blanca Garcia-Micò, Noelia Tarazona, Desamparados Roda, Josefa Castillo and Andres Cervantes

J. Pers. Med. 2022, 12(11), 1939; https://doi.org/10.3390/jpm12111939 - 21 Nov 2022

Cited by 8 | Viewed by 2074

Abstract

Precision medicine approaches for solid tumors are mainly based on genomics. Its employment in clinical trials has led to somewhat underwhelming results, except for single responses. Moreover, several factors can influence the response, such as gene and protein expression, the coexistence of different [...] Read more.

Precision medicine approaches for solid tumors are mainly based on genomics. Its employment in clinical trials has led to somewhat underwhelming results, except for single responses. Moreover, several factors can influence the response, such as gene and protein expression, the coexistence of different genomic alterations or post-transcriptional/translational modifications, the impact of tumor microenvironment, etc., therefore making it insufficient to employ a genomics-only approach to predict response. Recently, the implementation of patient-derived organoids has shed light on the possibility to use them to predict patient response to drug treatment. This could offer for the first time the possibility to move precision medicine to a functional environment. Full article

(This article belongs to the Special Issue The Present and Future of Personalized Medicine in Oncology)

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7 pages, 255 KiB

Open AccessPerspective

Steps towards a Multiple Myeloma Cure?

by Alessandro Gozzetti and Monica Bocchia

J. Pers. Med. 2022, 12(9), 1451; https://doi.org/10.3390/jpm12091451 - 03 Sep 2022

Cited by 3 | Viewed by 1778

Abstract

Multiple myeloma survival has increased in last 20 years because of new treatments, better clinical management due to novel diagnostic tools such as imaging, and better understanding of the disease, biologically and genetically. Novel drugs have been introduced that act with different therapeutic [...] Read more.

Multiple myeloma survival has increased in last 20 years because of new treatments, better clinical management due to novel diagnostic tools such as imaging, and better understanding of the disease, biologically and genetically. Novel drugs have been introduced that act with different therapeutic mechanisms, but so have novel therapeutic strategies such as consolidation and maintenance after autologous stem cell transplant. Imaging (such as PET-CT and MRI) has been applied at diagnosis and after therapy for minimal residual disease monitoring. Multiparametric flow and molecular NGS may detect, with high-sensitivity, residual monoclonal plasma cells in the bone marrow. With this novel therapeutic and biological approach, a considerable fraction of multiple myeloma patients can achieve durable remission or even MGUS-like regression, which can ultimately lead to disease disappearance. The big dogma, “Myeloma is an incurable disease”, is hopefully fading. Full article

(This article belongs to the Special Issue The Present and Future of Personalized Medicine in Oncology)

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