Targeting fusions for improved outcomes in oncology treatment

Mina Nikanjam1, Ryosuke Okamura1, Donald A Barkauskas2

  • 1Division of Hematology and Oncology, Center for Personalized Cancer Therapy, Moores Cancer Center, University of California at San Diego, San Diego, California.

Cancer
|December 4, 2019
PubMed
Abstract

Insights

Targeting gene fusions in cancer therapy significantly improves response rates and progression-free survival (PFS) compared to non-fusion targets. These findings highlight fusions as crucial therapeutic targets for optimized oncology treatments.

Area of Science:

  • Oncology
  • Genomics
  • Pharmacology

Background:

  • Gene fusions are increasingly recognized as critical targets in cancer therapy.
  • Understanding the therapeutic outcomes associated with targeting gene fusions versus non-fusion alterations is essential for advancing precision oncology.

Purpose of the Study:

  • To evaluate and compare treatment outcomes for patients with fusion targets versus those with non-fusion targets.
  • To assess the efficacy of US Food and Drug Administration (FDA)-approved single agents in patients with fusion-positive cancers.

Main Methods:

  • A retrospective analysis of 6189 patients treated with 28 FDA-approved drugs was conducted.
  • Outcomes were compared between patients with fusion targets and those with other genetic alterations.
  • A separate analysis included 79 patients with fusions treated at the University of California at San Diego.

Main Results:

  • Patients with fusion targets showed significantly higher response rates (68% vs. 50%) compared to non-fusion targets (odds ratio [OR], 1.67; P < .0001).
  • Solid tumor therapies had an OR of 2.07 (P < .0001) and hematologic therapies had an OR of 3.35 (P < .0001) for fusion targets.
  • Median progression-free survival (PFS) was longer for patients matched to fusions (11.6 months) versus unmatched (4.9 months) (P = .034).

Conclusions:

  • Targeting gene fusions demonstrates significantly higher response rates and improved PFS compared to non-fusion targets.
  • Fusions represent important therapeutic targets in oncology.
  • Further research is warranted to confirm the necessity of targeting fusions for optimized cancer therapy, even when other alterations are present.

Related Concept Videos

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...
8.6K
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...
5.8K
Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
1.7K
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...
3.6K
Cancer Vaccines01:30

Cancer Vaccines

Cancer treatment vaccines are a rapidly evolving field that offers a promising approach to immunotherapy. Unlike traditional vaccines that prevent diseases, cancer treatment vaccines are designed to treat existing cancers by stimulating the immune system to recognize and attack cancer cells.
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...
897
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...
9.7K