NEW DELHI : The “revolution in the understanding of cancer at the molecular level” has led to dramatic responses in cancer patients to new therapies that are targeted precisely at their particular type of tumours, according to Dr Kapil Dhingra, a member of the executive committee for the 28th EORTC-NCI-AACR [1] Symposium on Molecular Targets and Cancer Therapeutics that is taking place in Munich, Germany. “We are seeing an important shift in oncology as we move from a one-treatment-fits-all approach to an era of personalised medicine for cancer,” he says. Several new drugs that show dramatic efficacy in patients with very advanced disease who have failed standard therapies. “At the same time, advances in liquid biopsy technologies, in which blood is taken and analysed to detect genetic mutations, allow clinicians and researchers to obtain a real time portrait of the patients’ cancers and their responses to treatment in a non-invasive way, thereby ushering in a new era of cancer therapeutics,” he adds. Dr Dhingra, who is managing member of KAPital Consulting LLC (USA) spoke about the “remarkable anti-tumour activity” from an ongoing Phase I study of a new drug, BLU-285, that targets specific mutations in the cancer-causing genes that drive rare sarcomas (soft tissue cancer) of the digestive system (gastrointestinal stromal tumours or GISTs).
Dr Dhingra said: “Preliminary clinical efficacy has been seen, even at very low doses, and it is active in patients with advanced disease, many of whom had disease that had progressed on previous treatments. “Liquid biopsies showed a large reduction in circulating tumour DNA within two weeks of starting treatment.” Another new drug called DCC-2618 targets the same oncogenes (cancer-causing genes) in GIST as BLU-285, but a broader range of alterations in these genes. It is being tested in a phase I trial in patients with advanced GIST and other advanced cancers including one patient with glioblastoma multiforme (GBM) – one of the most common and aggressive forms of brain cancer. “DCC-2618 is well tolerated by patients and the anti-tumour activity observed to date suggest that it is effectively inhibiting the tyrosine kinases that we are targeting.” Dr Dhingra said that even though the phase I dose escalation is ongoing, impressive early results have been seen, including in the difficult-to-treat site of the brain.
“Liquid biopsies have revealed in real or near-real time the presence of multiple mutations, reflecting a diversity in the genetic make-up of the tumours that might have been missed even if an invasive tissue biopsy had been done, which is traditionally considered to be the ‘gold standard’.” Patient-friendly liquid biopsies, experts said, successfully identify molecular alterations that lead to drug resistance in nearly 80 per cent of patients. Professor Ryan Corcoran, Translational Research Director, Center for Gastrointestinal Cancers, Massachusetts General Hospital Cancer Center (USA), explained that circulating tumour DNA is shed by tumour cells throughout the body into the bloodstream and can be isolated from a routine blood draw. “One of the biggest advantages of liquid biopsies is that they can be performed from a routine blood draw, sparing patients the necessity of undergoing costly and invasive tumour biopsies, which can also pose some procedural risks for patients.” (AGENCIES)
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