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Cancers
Special Issues
Tissue Agnostic Drug Development in Cancer
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Tissue Agnostic Drug Development in Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Drug Development".

Deadline for manuscript submissions: closed (18 February 2024) | Viewed by 5035

Special Issue Editors

Dr. Shivaani Kummar

E-Mail Website
Guest Editor
Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA
Interests: developing new treatments for cancer
Dr. Kyaw Thein

E-Mail Website
Guest Editor
Comprehensive Cancer Centers of Nevada, Las Vegas, NV 89148, USA
Interests: phase 1 (investigational cancer therapeutics); thyroid; head and neck cancers

Special Issue Information

Dear Colleagues, 

The utilization of molecular genetics and biomarker-driven strategies for treatment selection has led to the concept of tissue-agnostic drug development. Histology-driven drug development has been the norm for decades, but recent advancements have focused efforts on tissue-agnostic drug development depending on the biological context. Regulatory approvals of larotrectinib and entrectinib for the treatment of neurotrophic tyrosine kinase (NTRK)-fusion-positive solid tumors, dabrafenib plus trametinib for unresectable or metastatic solid tumors with BRAFV600E mutations, and selpercatinib in the treatment of locally advanced or metastatic rearranged during transfection (RET) fusion-positive solid tumors are examples of targeted agents approved broadly across histologies. The tissue-agnostic regulatory approval of immunotherapies (for example, pembrolizumab for the treatment of unresectable or metastatic, microsatellite instability-high (MSI-H), or deficient mismatch repair (dMMR) solid tumors, and of tumor mutational burden-high (TMB-H) tumors; and dostarlimab-gxly for the treatment of mismatch-repair-deficient recurrent or advanced solid tumors) have further heightened interest in tissue-agnostic drug development.

This Special Issue will cover recent tissue-agnostic drug approvals, the emergence of drug resistance and strategies to overcome it, and lessons learned conducting multihistology trials in relatively rare subsets of cancers. Recent successes have created an exciting new avenue to approach drug development in cancer and improve outcomes for patients with a variety of tumors.

Dr. Shivaani Kummar
Dr. Kyaw Thein
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • tissue agnostic drug development
  • pembrolizumab
  • microsatellite instability-high (MSI-H)
  • tumor mutational burden-high (TMB-H)
  • dostarlimab-gxly
  • larotrectinib
  • entrectinib
  • neurotrophic tyrosine kinase (NTRK)-fusion-positive solid tumors
  • dabrafenib and trametinib
  • selpercatinib
  • rearranged during transfection (RET) gene fusion
  • precision medicine

Published Papers (3 papers)

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Review

19 pages, 893 KiB  
Review
Bayesian Methods for Information Borrowing in Basket Trials: An Overview
by Tianjian Zhou and Yuan Ji
Cancers 2024, 16(2), 251; https://doi.org/10.3390/cancers16020251 - 05 Jan 2024
Viewed by 972
Abstract
Basket trials allow simultaneous evaluation of a single therapy across multiple cancer types or subtypes of the same cancer. Since the same treatment is tested across all baskets, it may be desirable to borrow information across them to improve the statistical precision and [...] Read more.
Basket trials allow simultaneous evaluation of a single therapy across multiple cancer types or subtypes of the same cancer. Since the same treatment is tested across all baskets, it may be desirable to borrow information across them to improve the statistical precision and power in estimating and detecting the treatment effects in different baskets. We review recent developments in Bayesian methods for the design and analysis of basket trials, focusing on the mechanism of information borrowing. We explain the common components of these methods, such as a prior model for the treatment effects that embodies an assumption of exchangeability. We also discuss the distinct features of these methods that lead to different degrees of borrowing. Through simulation studies, we demonstrate the impact of information borrowing on the operating characteristics of these methods and discuss its broader implications for drug development. Examples of basket trials are presented in both phase I and phase II settings. Full article
(This article belongs to the Special Issue Tissue Agnostic Drug Development in Cancer)
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22 pages, 563 KiB  
Review
Challenges and Future Directions in the Management of Tumor Mutational Burden-High (TMB-H) Advanced Solid Malignancies
by Jibran Ahmed, Biswajit Das, Sarah Shin and Alice Chen
Cancers 2023, 15(24), 5841; https://doi.org/10.3390/cancers15245841 - 14 Dec 2023
Viewed by 1107
Abstract
A standardized assessment of Tumor Mutational Burden (TMB) poses challenges across diverse tumor histologies, treatment modalities, and testing platforms, requiring careful consideration to ensure consistency and reproducibility. Despite clinical trials demonstrating favorable responses to immune checkpoint inhibitors (ICIs), not all patients with elevated [...] Read more.
A standardized assessment of Tumor Mutational Burden (TMB) poses challenges across diverse tumor histologies, treatment modalities, and testing platforms, requiring careful consideration to ensure consistency and reproducibility. Despite clinical trials demonstrating favorable responses to immune checkpoint inhibitors (ICIs), not all patients with elevated TMB exhibit benefits, and certain tumors with a normal TMB may respond to ICIs. Therefore, a comprehensive understanding of the intricate interplay between TMB and the tumor microenvironment, as well as genomic features, is crucial to refine its predictive value. Bioinformatics advancements hold potential to improve the precision and cost-effectiveness of TMB assessments, addressing existing challenges. Similarly, integrating TMB with other biomarkers and employing comprehensive, multiomics approaches could further enhance its predictive value. Ongoing collaborative endeavors in research, standardization, and clinical validation are pivotal in harnessing the full potential of TMB as a biomarker in the clinic settings. Full article
(This article belongs to the Special Issue Tissue Agnostic Drug Development in Cancer)
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24 pages, 1461 KiB  
Review
RET-Altered Cancers—A Tumor-Agnostic Review of Biology, Diagnosis and Targeted Therapy Activity
by Antoine Desilets, Matteo Repetto, Soo-Ryum Yang, Eric J. Sherman and Alexander Drilon
Cancers 2023, 15(16), 4146; https://doi.org/10.3390/cancers15164146 - 17 Aug 2023
Cited by 2 | Viewed by 2145
Abstract
RET alterations, such as fusions or mutations, drive the growth of multiple tumor types. These alterations are found in canonical (lung and thyroid) and non-canonical (e.g., gastrointestinal, breast, gynecological, genitourinary, histiocytic) cancers. RET alterations are best identified via comprehensive next-generation sequencing, preferably with [...] Read more.
RET alterations, such as fusions or mutations, drive the growth of multiple tumor types. These alterations are found in canonical (lung and thyroid) and non-canonical (e.g., gastrointestinal, breast, gynecological, genitourinary, histiocytic) cancers. RET alterations are best identified via comprehensive next-generation sequencing, preferably with DNA and RNA interrogation for fusions. Targeted therapies for RET-dependent cancers have evolved from older multikinase inhibitors to selective inhibitors of RET such as selpercatinib and pralsetinib. Prospective basket trials and retrospective reports have demonstrated the activity of these drugs in a wide variety of RET-altered cancers, notably those with RET fusions. This paved the way for the first tumor-agnostic selective RET inhibitor US FDA approval in 2022. Acquired resistance to RET kinase inhibitors can take the form of acquired resistance mutations (e.g., RET G810X) or bypass alterations. Full article
(This article belongs to the Special Issue Tissue Agnostic Drug Development in Cancer)
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