Arginine deprivation as a new treatment strategy for head and neck cancer

Cheng-Chih Huang1, Sen-Tien Tsai, Ching-Chuan Kuo

  • 1Department of Otolaryngology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Oral Oncology
|August 25, 2012
PubMed
Abstract

Insights

Argininosuccinate synthetase (ASS) high expression predicts poor survival in head and neck cancer. Arginine deprivation therapy shows promise for treating these cancers.

Area of Science:

  • Oncology
  • Cancer Biology
  • Biochemistry

Background:

  • Arginine is a nonessential amino acid crucial for tumor growth.
  • Argininosuccinate synthetase (ASS) is the key enzyme in arginine synthesis.
  • The role of ASS and arginine deprivation therapy in head and neck cancer remains unexplored.

Purpose of the Study:

  • To investigate the expression of ASS in head and neck cancers.
  • To evaluate the efficacy of arginine deprivation therapy in head and neck cancer models.
  • To determine the prognostic value of ASS in oral squamous cell carcinoma (OSCC).

Main Methods:

  • Assessed growth inhibition of head and neck cancer cells using arginine-free medium and arginine deiminase (ADI).
  • Immunohistochemically analyzed tumor ASS status in 73 OSCC patients.
  • Correlated ASS status with clinicopathological parameters and patient survival.

Main Results:

  • Arginine deprivation significantly inhibited head and neck cancer cell proliferation.
  • ADI treatment demonstrated varying degrees of growth inhibition across cell lines.
  • High tumor ASS levels independently predicted unfavorable disease-free survival in OSCC patients.
  • Knockdown of ASS enhanced ADI's growth-inhibitory effect.

Conclusions:

  • Elevated tumor ASS expression is a significant independent predictor of poor disease-free survival in OSCC.
  • Arginine deprivation therapy presents a potential novel therapeutic strategy for head and neck cancers.

Related Concept Videos

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...
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...
Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists01:28

Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists

Neurokinin 1 (NK1) receptors are distributed across the GI tract, vagal afferents, and key CNS regions including the central vomiting center and chemoreceptor trigger zone (CTZ) Chemotherapy agents stimulate enterochromaffin cells in the gastrointestinal (GI) tract to release large amounts of substance P (SP). SP is a neuropeptide released by specific sensory nerves in response to many different stressors, including those in the GI mucosa affected by chemotherapy.  SP binds and activates these...
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 specific...