The reality of early-onset colorectal cancer: highlighting the needs in a unique but emerging population

Rogers, Jane E.; Johnson, Benny

doi:10.21037/dmr-21-77

Cited by 9 publications

(6 citation statements)

References 20 publications

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“…Young adults and adolescents with cancer can present with needs that are different from those of their adult and pediatric counterparts. 243 , 244 They may experience similar side effects, but these symptoms may have a greater impact on daily activities including work and childcare. 245 Furthermore, younger patients also have unique psychosocial and informational needs, including those that concern educational/work pursuits and goals.…”

Section: Resultsmentioning

confidence: 99%

“…245 Furthermore, younger patients also have unique psychosocial and informational needs, including those that concern educational/work pursuits and goals. 243 There may also be more difficulties in the management of symptoms, fears, and behavior modifications. 246 There were 2 LE 4 studies concerning the organization of supportive care programs among individuals with eoCRC, including the management of sleeping, sexual, intimacy, nutritional, and social care.…”

Section: Session Vi: Treatment (T)mentioning

confidence: 99%

See 1 more Smart Citation

Delphi Initiative for Early-Onset Colorectal Cancer (DIRECt) International Management Guidelines

Giulia

Mannucci

Balaguer

et al. 2023

Clinical Gastroenterology and Hepatology

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Section: Resultsmentioning

confidence: 99%

Section: Session Vi: Treatment (T)mentioning

confidence: 99%

Delphi Initiative for Early-Onset Colorectal Cancer (DIRECt) International Management Guidelines

Giulia

Mannucci

Balaguer

et al. 2023

Clinical Gastroenterology and Hepatology

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“…Over the last 25 years, the incidence of early onset CRC has been steadily increasing ( 24 ). Indeed, substantial increment of CRC incidence in 20-34 year old men and women is estimated to take place by 2030 ( 25 ). Early onset CRC is typically diagnosed at an advanced stage and characterized by rapid progression, mucinous or signet ring histology (HGM/SR-CRC) and lower differentiation ( 26 ).…”

Section: Discussionmentioning

confidence: 99%

Case report: Preclinical efficacy of NEDD8 and proteasome inhibitors in patient-derived models of signet ring high-grade mucinous colorectal cancer from a Lynch syndrome patient

et al. 2023

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High-grade mucinous colorectal cancer (HGM CRC) is particularly aggressive, prone to metastasis and treatment resistance, frequently accompanied by “signet ring” cancer cells. A sizeable fraction of HGM CRCs (20-40%) arises in the context of the Lynch Syndrome, an autosomal hereditary syndrome that predisposes to microsatellite instable (MSI) CRC. Development of patient-derived preclinical models for this challenging subtype of colorectal cancer represents an unmet need in oncology. We describe here successful propagation of preclinical models from a case of early-onset, MSI-positive metastatic colorectal cancer in a male Lynch syndrome patient, refractory to standard care (FOLFOX6, FOLFIRI-Panitumumab) and, surprisingly, also to immunotherapy. Surgical material from a debulking operation was implanted in NOD/SCID mice, successfully yielding one patient-derived xenograft (PDX). PDX explants were subsequently used to generate 2D and 3D cell cultures. Histologically, all models resembled the tumor of origin, displaying a high-grade mucinous phenotype with signet ring cells. For preclinical exploration of alternative treatments, in light of recent findings, we considered inhibition of the proteasome by bortezomib and of the related NEDD8 pathway by pevonedistat. Indeed, sensitivity to bortezomib was observed in mucinous adenocarcinoma of the lung, and we previously found that HGM CRC is preferentially sensitive to pevonedistat in models with low or absent expression of cadherin 17 (CDH17), a differentiation marker. We therefore performed IHC on the tumor and models, and observed no CDH17 expression, suggesting sensitivity to pevonedistat. Both bortezomib and pevonedistat showed strong activity on 2D cells at 72 hours and on 3D organoids at 7 days, thus providing valid options for in vivo testing. Accordingly, three PDX cohorts were treated for four weeks, respectively with vehicle, bortezomib and pevonedistat. Both drugs significantly reduced tumor growth, as compared to the vehicle group. Interestingly, while bortezomib was more effective in vitro, pevonedistat was more effective in vivo. Drug efficacy was further substantiated by a reduction of cellularity and of Ki67-positive cells in the treated tumors. These results highlight proteasome and NEDD8 inhibition as potentially effective therapeutic approaches against Lynch syndrome-associated HGM CRC, also when the disease is refractory to all available treatment options.

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“…Patients diagnosed at a younger age may have to process a cancer diagnosis that feels unexpected compared with what their peers may be experiencing. 103 Another important difference is the potential need for fertility preservation in young patients diagnosed with EOCRC. 104 Surgery, chemotherapy, and pelvic radiation all may affect a patient's fertility temporarily or permanently.…”

Section: Treatment Considerations For Eocrcmentioning

confidence: 99%

The Molecular Genetics of Colorectal Cancer, Hereditary Colorectal Cancer Syndromes, and Early-Onset Colorectal Cancer

Sommovilla

2022

Digestive Disease Interventions

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While the incidence of colorectal cancer is decreasing for adults older than 50 years, there is a rise in colorectal cancer among individuals younger than 50 (termed early-onset colorectal cancer). This increase is multifactorial and reflects differences in screening, changes in environmental factors, and other influences. In this article, we review the molecular and genetic basis of sporadic colorectal cancer as well as inherited colorectal cancer syndromes. We also summarize the epidemiology of early-onset colorectal cancer and considerations for the treatment of this population of patients.

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The reality of early-onset colorectal cancer: highlighting the needs in a unique but emerging population

Cited by 9 publications

References 20 publications

Delphi Initiative for Early-Onset Colorectal Cancer (DIRECt) International Management Guidelines

Delphi Initiative for Early-Onset Colorectal Cancer (DIRECt) International Management Guidelines

Case report: Preclinical efficacy of NEDD8 and proteasome inhibitors in patient-derived models of signet ring high-grade mucinous colorectal cancer from a Lynch syndrome patient

The Molecular Genetics of Colorectal Cancer, Hereditary Colorectal Cancer Syndromes, and Early-Onset Colorectal Cancer

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