Targeted therapy for upper gastrointestinal tract cancer: current and future prospects
Related Experiment Video
Updated: Nov 23, 2025
Author Spotlight: Advancing Early Detection and Treatment of Gastrointestinal Tumors
Published on: February 16, 2024
Matthew W Rosenbaum1, Raul S Gonzalez1
1Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Abstract:
Gastric and oesophageal carcinoma remain major causes of worldwide mortality and morbidity. Despite incredible progress in understanding tumour biology, few targeted treatment options have proved effective in prolonging survival, and adjuvant therapy is largely interchangeable in these carcinomas. Through large-scale sequencing by the Cancer Genome Atlas and the Asian Cancer Research Group, numerous potential molecular targets have been discovered. Of the approved targeted therapies for gastric and oesophageal cancer, pathologists play a role in patient selection for the majority of them. Trastuzumab has been approved as a first-line therapy in conjunction with standard treatment in adenocarcinomas with either 3+ HER2/neu expression by immunohistochemistry or ERBB2 amplification by FISH. PD-L1 immunohistochemistry showing a combined positive score of 1 or greater qualifies patients for third-line pembrolizumab therapy, and identification of microsatellite instability-high carcinomas may qualify patients for second-line pembrolizumab. Ramucirumab, targeting VEGFR2, has also been approved for second-line therapy in gastric carcinoma. Non-surgical therapy for gastrointestinal stromal tumours relies mainly upon tyrosine kinase inhibitors, while new targeted therapy options for neuroendocrine neoplasms have recently emerged. Potential future options for targeted therapy in all these malignancies are being investigated in clinical trials, as this review will discuss.
Insights
Gastric and esophageal cancers are deadly, but targeted therapies are emerging. Pathologists are key in selecting patients for treatments like trastuzumab and pembrolizumab, improving survival for these difficult cancers.
Area of Science:
- Oncology
- Molecular Pathology
- Gastrointestinal Cancer Research
Background:
- Gastric and esophageal carcinomas are significant global health burdens with limited effective targeted treatments.
- Advances in cancer genomics have identified numerous potential molecular targets for these malignancies.
- Current adjuvant therapies for these cancers are largely interchangeable.
Purpose of the Study:
- To review approved targeted therapies for gastric and esophageal cancers.
- To highlight the role of pathologists in patient selection for targeted treatments.
- To discuss emerging and future targeted therapy options for these gastrointestinal malignancies.
Main Methods:
- Review of large-scale sequencing data from Cancer Genome Atlas and Asian Cancer Research Group.
- Analysis of approved targeted therapies including trastuzumab, pembrolizumab, and ramucirumab.
- Examination of diagnostic criteria used for patient selection (e.g., HER2/neu, PD-L1, MSI-H).
Main Results:
- Trastuzumab is approved for HER2-positive (HER2/neu 3+ or ERBB2 amplification) adenocarcinomas.
- Pembrolizumab is indicated for PD-L1 positive (CPS ≥1) or microsatellite instability-high (MSI-H) advanced gastric/esophageal cancers.
- Ramucirumab is an approved second-line therapy for gastric carcinoma targeting VEGFR2.
Conclusions:
- Pathological assessment is crucial for guiding targeted therapy selection in gastric and esophageal cancers.
- Several targeted therapies have demonstrated efficacy, improving patient outcomes.
- Ongoing clinical trials are exploring novel targeted treatment strategies for these cancers.
More Related Videos
10:28Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT
Published on: January 22, 2018
08:59Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down
Published on: December 11, 2017
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:26Peptic Ulcer Disease IV: Management
The therapeutic approach involves ensuring adequate rest, implementing drug therapy, promoting smoking cessation, making dietary modifications, and emphasizing long-term follow-up care.
Pharmacological management
The prevailing therapy for peptic ulcers involves a combination of managing the patient's current...
01:30Cancer Vaccines
Cancer vaccines come in two categories: preventive (prophylactic) and treatment (active). Preventive vaccines, such as the Human Papillomavirus (HPV) vaccine, protect against viruses that cause certain...
02:56Treatment Resistant Cancers
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...