Related Experiment Video

Updated: Jul 13, 2025

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
08:46

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms

Published on: December 9, 2015

10.6K

Quantifying the Expanding Landscape of Clinical Actionability for Patients with Cancer

Sarah P Suehnholz1,2, Moriah H Nissan1,2, Hongxin Zhang1

  • 1Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.

Cancer Discovery
|October 18, 2023
PubMed

Insights

Precision oncology has significantly expanded clinical actionability in solid tumors between 2017 and 2022. Despite progress, many cancers still lack actionable targets, highlighting the need for novel therapies.

Area of Science:

  • Oncology
  • Genomics
  • Translational Medicine

Background:

  • Precision oncology aims to tailor cancer treatments based on molecular profiles.
  • Defining clinically actionable molecular alterations is crucial for patient benefit.
  • The landscape of actionable targets in cancer is rapidly evolving.

Purpose of the Study:

  • To quantify the change in clinical actionability of solid tumors over a five-year period.
  • To assess the impact of evolving knowledge bases on treatment selection.
  • To identify frequently altered genes in tumors lacking standard care biomarkers.

Main Methods:

  • Analysis of 47,271 solid tumors sequenced using the MSK-IMPACT assay.
  • Comparison of tumor molecular alterations against two versions of the OncoKB knowledge base (2017 vs. 2022).
  • Categorization of alterations based on clinical actionability levels (standard care vs. nonactionable).

Main Results:

  • The proportion of tumors with standard care predictive biomarkers increased from 8.9% to 31.6% (2017-2022).
  • The fraction of tumors with nonactionable drivers decreased from 44.2% to 22.8%.
  • TP53, KRAS, and CDKN2A were the most frequent alterations in tumors with limited actionability.

Conclusions:

  • Clinical actionability in precision oncology has substantially increased due to knowledge base advancements.
  • A significant unmet need persists for novel therapies targeting undruggable oncogenic drivers.
  • Continued research is vital to expand therapeutic options for all cancer patients.

More Related Videos

Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo09:19

Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo

Published on: February 6, 2015

8.7K
Author Spotlight: Improving Radiation Therapy Access with Radiation Planning Assistant05:18

Author Spotlight: Improving Radiation Therapy Access with Radiation Planning Assistant

Published on: October 6, 2023

1.4K

Related Concept Videos

Cancer Survival Analysis01:21

Cancer Survival Analysis

Cancer survival analysis focuses on quantifying and interpreting the time from a key starting point, such as diagnosis or the initiation of treatment, to a specific endpoint, such as remission or death. This analysis provides critical insights into treatment effectiveness and factors that influence patient outcomes, helping to shape clinical decisions and guide prognostic evaluations. A cornerstone of oncology research, survival analysis tackles the challenges of skewed, non-normally...
357
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
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...
4.9K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
7.7K
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.3K
Types of Biopharmaceutical Studies: Controlled and Non-Controlled Approaches01:23

Types of Biopharmaceutical Studies: Controlled and Non-Controlled Approaches

Biopharmaceutical studies constitute a vital field aiming to enhance drug delivery methods and refine therapeutic approaches, drawing upon diverse interdisciplinary knowledge. In research methodologies, the choice between controlled and non-controlled studies significantly influences the study's reliability and accuracy.
Non-controlled studies, commonly employed for initial exploration, lack a control group, rendering them susceptible to biases and external influences. In contrast,...
133
Cancer Therapies02:49

Cancer Therapies

Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
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...
7.7K