Sendurai Mani, Associate Director of Translational Oncology at Legorreta Cancer Center, shared on LinkedIn:
“Cancer is not static. It evolves, adapts, and sometimes changes its identity to survive treatment.
I am delighted to share our newly published article,՛Cancer Plasticity and Histological Transformation as Adaptive Resistance Mechanisms in Precision Oncology՛ published in the journal Med from Cell Press journal.
Special thanks to my wonderful colleague and co-corresponding author, Dr. Vivek Subbiah, whose passion for precision oncology and dedication to improving patient care continue to inspire me.
It has been a pleasure working together to bridge fundamental cancer biology and clinical oncology.
I am also grateful to the first author Nick Kuburich and our outstanding co-authors, Mohamed A. Gouda, Breanna Demestichas, Preetesh Jain, Petra den Hollander, Yakirevich Evgeny, Razelle Kurzrock, and Wafik El-Deiry, for their invaluable contributions.
Precision oncology has transformed cancer treatment by targeting specific molecular alterations.
However, cancer cells are remarkably adaptable.
Even when we successfully target their genetic vulnerabilities, they can escape treatment by changing their cellular identity, adopting alternative cell states, or undergoing histological transformation.
This raises an important question: Are we targeting what cancer is today while overlooking what it can become tomorrow?
Cancer plasticity challenges the traditional view that genetic mutations alone determine therapeutic response.
Understanding how tumor cells adapt and change their identity may be essential to developing more durable treatments.
I believe the next frontier of precision oncology must move beyond identifying actionable mutations to understanding and anticipating tumor evolution, cellular plasticity, and mechanisms of therapeutic resistance.
The ultimate goal is not simply to achieve an initial response, but to prevent cancer from finding another way to survive.
The article is freely accessible through December 2, 2026, using the link below.
No registration or subscription is required.
I welcome your thoughts on how we can better integrate cancer plasticity into precision oncology strategies.”
Title: Cancer plasticity and histological transformation as adaptive resistance mechanisms in precision oncology
Authors: Nick A. Kuburich, Mohamed A. Gouda, Breanna R. Demestichas, Preetesh Jain, Petra den Hollander, Evgeny Yakirevich, Razelle Kurzrock, Wafik S. El-Deiry, Sendurai A. Mani, Vivek Subbiah
Vivek Subbiah, Chief of Early-Phase Drug Development at the Sarah Cannon Research Institute, added:
“Amazing to work on this review published in Med by Cell Press.
It started with a clinical question.
One of my patients’ glioblastoma transformed into gliosarcoma after treatment with BRAF and MEK inhibitor.
Another patient’s NSCLC adenocarcinoma became small cell lung cancer after RET inhibitor.
A third patient’s papillary thyroid cancer turned into anaplastic thyroid cancer again after BRAF inhibitor.
Dr. Gouda and I started something from a clinical point of view. But we wanted more in depth answers.
Over coffee at an American Association for Cancer Research meeting, I asked the guru of EMT biology Sendurai Mani this question and to look at this from the basic science/translational point of view.
From that conversation, a comprehensive search and this review were born.
Wonderful to work with his team on this one.
It took around 2 years to get this done but learned a lot on this.
If we want the next generation of cancer therapies to last, we have to treat cancer as an evolving system, not a static target.”
Other articles about adaptive resistance on OncoDaily.