Related Experiment Video

Updated: Sep 27, 2025

Establishment of a Primary Culture of Patient-derived Soft Tissue Sarcoma
07:55

Establishment of a Primary Culture of Patient-derived Soft Tissue Sarcoma

Published on: April 11, 2018

14.6K

Soft Tissue Sarcoma Study: Association of Genetic Alterations in the Apoptosis Pathways with Chemoresistance to

Evgeny M Kirilin1, Timur I Fetisov2, Natalia I Moiseeva2

  • 1Belozersky Institute of Physicochemical Biology, Lomonosov Moscow State University, Lenin Hills 1, 119991 Moscow, Russia.

Cancers
|April 12, 2022
PubMed

Insights

Genetic alterations in apoptotic signaling pathways are linked to chemoresistance in soft tissue sarcomas (STS). Understanding these changes can guide personalized therapy for STS patients, improving treatment outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Soft tissue sarcomas (STS) are diverse cancers with over 100 subtypes, complicating personalized treatment.
  • Current chemotherapy for advanced STS, including Doxorubicin/Ifosfamide or Gemcitabine/Docetaxel, benefits less than 50% of patients and often leads to drug resistance.

Purpose of the Study:

  • To investigate genetic alterations in cancer cells associated with chemoresistance in undifferentiated pleomorphic and synovial sarcomas.
  • To identify specific genetic targets within apoptotic signaling pathways that correlate with resistance to genotoxic chemotherapy.

Main Methods:

  • In vitro analysis of chemoresistance using primary STS cell cultures.
  • Genetic analysis of apoptotic signaling pathway components in tumor specimens.
  • Correlation of identified genetic alterations with response to Doxorubicin treatment.

Main Results:

  • Genetic alterations were identified in 27% of STS tumors, specifically in genes such as TP53, ATM, PIK3CB, PIK3R1, NTRK1, and CSF2RB.
  • STS cells with these genetic alterations exhibited resistance to Doxorubicin, with a notable exception for a specific TP53 mutation (Leu344Arg) that retained partial function.
  • A significant association was found between alterations in apoptotic signaling components and Doxorubicin chemoresistance.

Conclusions:

  • Alterations in apoptotic signaling pathways are significantly associated with chemoresistance in soft tissue sarcomas.
  • These findings are crucial for developing targeted therapeutic strategies for STS patients with specific genetic profiles.
  • Identifying these genetic alterations can pave the way for more effective and personalized treatment approaches for STS.
Keywords:
DocetaxelDoxorubicinGemcitabineIfosfamideapoptotic signalingchemoresistancegenetic alterationssoft tissue sarcomasynovial sarcomaundifferentiated pleomorphic sarcoma

More Related Videos

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts10:27

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Published on: July 25, 2020

7.4K
Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down08:59

Looking 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

7.3K

Related Concept Videos

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...
5.1K
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...
3.4K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.9K
Tumor Progression02:07

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
6.5K