Researchers at Punjabi University, Patiala have made significant progress towards making chemotherapy more effective by discovering new molecules to combat drug resistance mechanisms in cancer treatment. The study, published in the International Journal of Biological Macromolecules, addresses the issue of overcoming chemoresistance by drug-metabolizing enzymes (DMEs), which typically renders the chemotherapy ineffective.Key Highlights:
Breakthrough to Combat Chemoresistance:

• The study addresses the role of Phase-1 and Phase-2 DMEs in inactivating anti-cancer drugs, leading to drug resistance and treatment failure.

• Researchers designed new molecules to target DMEs to restore chemotherapy to its original strength and improve cancer survival rates.

Specific attention to Cyclophosphamide (CP):

• The study specifically studied cyclophosphamide (CP), a standard chemotherapeutic drug used to treat ovarian, breast, and blood cancers.

• The ALDH1A1 enzyme was identified as a major reason for CP drug resistance.

Discovery of ALDH1A1 Inhibitors:

• Two selective ALDH1A1 inhibitors were discovered, both of which are clinically approved and have established safety profiles.

• Co-treatment of ALDH1A1 inhibitors with CP significantly enhanced cancer cell sensitivity to chemotherapy, particularly in ALDH1A1 overexpressing cancer cells.

Implications for Precision Medicine:

• The study confirms that personalized cancer therapy may be possible based on the genetic and biochemical profile of the patient.

• Repurposed ALDH1A1 inhibitors can be utilized as adjuvants in CP-based chemotherapy, a cost-effective and safe approach to combat drug resistance.

Quotes from Researchers:
Prof. Om Silakari, Department of Pharmaceutical Sciences and Drug Research, Punjabi University:
"Chemoresistance is a critical global issue. By targeting drug-metabolizing enzymes like ALDH1A1, we can enhance the availability of the drug, reduce resistance, and enhance outcomes in cancer therapy."Gera Narinder, ICMR Senior Research Fellow, Punjabi University:
"Our research provides strong evidence that ALDH1A1 inhibitors can be effective adjuncts to cyclophosphamide chemotherapy and significantly improve patient outcomes."The research provides strong evidence for the therapeutic potential of combining ALDH1A1 inhibitors with traditional chemotherapy to overcome drug resistance. By providing a precision medicine approach, the discovery paves the way for more effective, targeted cancer treatments and improved survival rates. The findings have the potential to transform chemotherapy protocols and enhance the quality of life for cancer patients.