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PURPOSE OF REVIEW: Overall, the review underscores the evolving landscape of KRAS-targeted therapy and the potential for these approaches to improve outcomes for patients with gastrointestinal malignancies. It highlights the importance of ongoing research and clinical trials in advancing precision medicine strategies for KRAS-driven cancers. This review provides a comprehensive overview of the RAS signaling pathway and its significance in gastrointestinal malignancies. RECENT FINDINGS: The introduction of KRAS inhibitor represents a significant advancement in the treatment landscape for KRAS-mutant cancers. In this review, we discuss upcoming trends in KRAS-targeted therapy, including the development of mutant-specific direct KRAS inhibitors like MRTX1133 and pan-RAS inhibitors such as RMC-6236. It also explores indirect RAS inhibitors targeting upstream and downstream components of the RAS pathway. Additionally, the review examines other upcoming strategies like combination therapies, such as CDK4/6 and ERK MAPK inhibitors, as well as adoptive cell therapy and cancer vaccines targeting KRAS-mutant cancers. SUMMARY: Targeting RAS has become an important strategy in treating gastrointestinal cancer. These findings in this review underscore the importance of a multidisciplinary approach, integrating advances in molecular profiling, targeted therapy, immunotherapy, and clinical research to optimize treatment strategies for patients with KRAS-mutant gastrointestinal malignancies.
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Neoplasias Gastrointestinais , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/terapia , Neoplasias Gastrointestinais/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Terapia de Alvo Molecular , MutaçãoRESUMO
BACKGROUND: Telehealth modalities were introduced during the SARS-CoV-2 pandemic to assure continuation of cancer care and maintain social distance. METHODS: This is a retrospective cohort analysis of our telehealth expansion programme. We adapted two existing patient-reported outcome (PRO) telemonitoring tools that register and (self-)manage toxicities to therapy, while screening for SARS-CoV-2-related symptoms. Outpatients from a tertiary cancer centre were enrolled. The adapted PRO interface allowed for uniform registration of SARS-CoV-2-related symptoms and effective triage of patients at home where we also implemented systematic throat washings, when available. RESULTS: Three hundred and sixty patients registered to the telemonitoring systems from March 13 to May 15, 2020. Four prespecified SARS-CoV-2 alarms resulted in three patients with positive PCR testing. Other Covid-19 symptoms (fever 5× and cough 2×) led to pretreatment triage resulting in 1 seroconversion after initial negative testing. One of the 477 throat washings proved positive. CONCLUSIONS: The rapid adoption of an amended PRO (self-)registrations and toxicity management system was feasible and coordinated screening for Covid-19. Continued clinical cancer care was maintained, with significant decreased waiting time. The systemic screening with throat washings offered no real improvement.
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COVID-19/diagnóstico , Neoplasias/diagnóstico , Pandemias , SARS-CoV-2/patogenicidade , Adulto , COVID-19/complicações , COVID-19/virologia , Feminino , Humanos , Masculino , Programas de Rastreamento , Oncologia/tendências , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/virologia , SARS-CoV-2/genética , Telemedicina/tendênciasRESUMO
BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has overwhelmed the capacity of healthcare systems worldwide. Cancer patients, in particular, are vulnerable and oncology departments drastically needed to modify their care systems and established new priorities. We evaluated the impact of SARS-CoV-2 on the activity of a single cancer center. METHODS: We performed a retrospective analysis of (i) volumes of oncological activities (2020 vs 2019), (ii) patients' perception rate of the preventive measures, (iii) patients' SARS-CoV-2 infections, clinical signs thereof, and (iv) new diagnoses made during the SARS-CoV-2 pandemic. RESULTS: As compared with a similar time frame in 2019, the overall activity in total numbers of outpatient chemotherapy administrations and specialist visits was not statistically different (P = .961 and P = .252), while inpatient admissions decreased for both medical oncology and thoracic oncology (18% (P = .0018) and 44% (P < .0001), respectively). Cancer diagnosis plummeted (-34%), but no stage shift could be demonstrated.Acceptance and adoption of hygienic measures was high, as measured by a targeted questionnaire (>85%). However, only 46.2% of responding patients regarded telemedicine, although widely deployed, as an efficient surrogate to a consultation.Thirty-three patients developed SARS-CoV-2, 27 were hospitalized, and 11 died within this time frame. These infected patients were younger, current smokers, and suffered more comorbidities. CONCLUSIONS: This retrospective cohort analysis adds to the evidence that continuation of active cancer therapy and specialist visits is feasible and safe with the implementation of telemedicine. These data further confirm the impact of SARS-CoV-2 on cancer care management, cancer diagnosis, and impact of infection on cancer patients.
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COVID-19/epidemiologia , Institutos de Câncer/organização & administração , Institutos de Câncer/estatística & dados numéricos , Neoplasias/epidemiologia , Neoplasias/terapia , Fatores Etários , Comorbidade , Ciclopentanos , Humanos , Controle de Infecções/organização & administração , Neoplasias/diagnóstico , Neoplasias/mortalidade , Compostos de Organossilício , Pandemias , Percepção , Estudos Retrospectivos , SARS-CoV-2RESUMO
Colorectal cancer (CRC) remains a significant health burden globally, being the second leading cause of cancer-related mortality. Despite significant therapeutic advancements, resistance to systemic antineoplastic agents remains an important obstacle, highlighting the need for innovative screening tools to tailor patient-specific treatment. This review explores the application of patient-derived tumor organoids (PDTOs), three-dimensional, self-organizing models derived from patient tumor samples, as screening tools for drug resistance in CRC. PDTOs offer unique advantages over traditional models by recapitulating the tumor architecture, cellular heterogeneity, and genomic landscape and are a valuable ex vivo predictive drug screening tool. This review provides an overview of the current literature surrounding the use of PDTOs as an instrument for predicting therapy responses in CRC. We also explore more complex models, such as co-cultures with important stromal cells, such as cancer-associated fibroblasts, and organ-on-a-chip models. Furthermore, we discuss the use of PDTOs for drug repurposing, offering a new approach to identify the existing drugs effective against drug-resistant CRC. Additionally, we explore how PDTOs serve as models to gain insights into drug resistance mechanisms, using newer techniques, such as single-cell RNA sequencing and CRISPR-Cas9 genome editing. Through this review, we aim to highlight the potential of PDTOs in advancing our understanding of predicting therapy responses, drug resistance, and biomarker identification in CRC management.